|
Research >>> |
|
June/July 2010
Clinical
trial on deferiprone seeking patients; hoping for April 2011 launch A
long-awaited clinical trial to test deferiprone as a safe treatment for
NBIA is seeking patients interested in participating at Children’s
Hospital and Research Center in Oakland, Calif. Dr.
Elliott Vichinsky, chief of the hospital’s hematology/oncology
department, and his nurse associate, Nancy Sweeters, hope to enroll 20
to 30 patients in the trial. Those patients would need to make four
visits to Oakland, once every three months. The visits will be at study
start, 3 months, 6 months and 1 year. Dr.
Vichinsky and his team will be submitting the grant to the National
Institute of Neurological Disorders and Stroke (NINDS) which is a branch
of the National Institute (NIH) for a July 14 deadline. In this grant
they require that the group shows there is interest in the patient
population to go forward with this study. There is no personal
information that is sent into NINDS – just age, gender and state of
residence. If
all goes well the trial would launch in April 201. ApoPharma,
the maker of deferiprone, which is an iron chelator, will provide the
medication and placebo for the study. However, ApoPharma is not funding
the study. Vichinsky and his team originally thought that might happen,
but the company is looking at many other studies involving diseases with
brain iron. Consequently,
Vichinsky is seeking a $1 million grant from the National Institutes of
Health. Although the NIH did not fund his application last year,
Vichinsky believes his chances this year are improved. He received
Investigational New Drug (IND) approval from the Food and Drug
Administration in December 2009, a requirement before a study can begin.
This approval was based on a placebo-controlled study being done, a
change from the initial application. “Having the IND should put us
ahead of the pack,” Sweeters said. Anyone
who is interested in taking part in the study should contact Sweeters,
and those who want to show support for the grant through NIH’s
National Institute of Neurological Disorders and Stroke are asked to
call or e-mail the agency. As a patient advocacy group, NBIA Disorders
Association is supporting the application and preparing a letter
families can sign, especially those interested in taking part in this
study. Vichinsky
said grant applications will be peer-reviewed this fall and he hopes to
hear by November if the work will be funded beginning next April. Deferiprone
is an iron-removing drug able to cross the brain blood barrier. In the
study participants would be taking deferiprone orally. Deferiprone
was approved in 1999 by the European drug regulatory authority and can
be freely used in 48 countries. But it is still considered experimental
in the U.S. and is tightly regulated, although it has been used by
Vichinsky and others to treat complications of the blood disease
thalassemia since 2006. In
the past, other iron chelators had been tried with NBIA patients but
those attempts failed because individuals would become anemic and
treatment had to be stopped. A 2007 French study on Friedreich’s
Ataxia (FA), another disorder with excess iron in the brain, found that
deferiprone was effective in sweeping out the iron and improving
symptoms. That caused some NBIA families to wonder whether the drug
could also help their loved ones. Vichinsky
has been using the drug for thalassemia patients since 2006, and in
November 2007, my son Brent Bonfiglio of Fremont, Calif., became the
first U.S. child to receive deferiprone for NBIA in an FDA-approved
compassionate-use clinical trial under the direction of Vichinsky.
That protocol allows an experimental drug to be used on a
case-by-case basis on very sick individuals who have no other options.
He now cares for two other NBIA children, besides Brent, with
deferiprone. Brent
currently receives 35mg/kg/day.
Vichinsky said he would start doses in the clinical trial at 20
mg/kg and go no higher than 30 mg/kg a day. I
saw Brent, now 17, gradually improve from the drug. Sometimes I would
notice something very clearly, like Brent being able to sit without any
back support; other times it was more subtle. Regardless, I believe
deferiprone put the brakes on NBIA and that my son is better today than
he was three years ago. Adam
Tifone, 19, of Gibsonia, Penn., has been on deferiprone for two years.
His dosage started at slightly less than 20 mg/kg/day for the first
eight months, according to his father, Rick Tifone. He was stable during
that period, but his family saw a noticeable improvement in his balance
when the dosage was boosted to 26 mg/kg/day, Rick Tifone said. “The balance
improvement lasted until early 2010,” Rick Tifone said in late May.
“Three weeks ago his dosage was increased to 35/mg/day. We haven’t
yet seen any noticeable improvement at this higher dosage. He has not
had any side effects from the drug in the two years he has been on it.
Overall, I would say his condition is about the same as it was two years
ago, which given the degenerative nature of this disease, the
deferiprone treatment has been a success.” I
know of about 10 other NBIA patients undergoing treatment in the U.S.,
Cuba, the UK and Italy where Dr. Gian Luca Forni of Centro della
Microcitemia, Ospedale Galliera, Genoa was the first to treat NBIA
patients with deferiprone. Results
to date have been encouraging. Last
year, nine PKAN patients in Italy completed a six-month trial with Drs.
Bertini and Nardocci using a dosage of 25 mg/kg/day and tolerated
deferiprone well. Publication of those results are still pending. It’s
possible that some patients may not benefit, and deferiprone has
well-known side effects. Safety data has been collected from about 1,000
patients, including 500 who have been on the drug for at least two
years. The
most common side effects are reddish discoloration of the urine, nausea,
vomiting, joint pain, abdominal pain and an increase in ALT, an enzyme
that measures liver function. In general, those reactions were mild to
moderate and generally go away without stopping deferiprone. A
major side effect is lowered white blood cell count, known as
“neutropenia” or “agranulocytosis,” depending on the severity.
That side effect was seen in about 1 percent of patients and went away
when deferiprone was stopped. A low white cell count puts you at risk
for serious infection and must be promptly treated. At
the 2009 NBIA Family Conference, Dr. Penny Hogarth, a neurologist and
associate professor at the Oregon Health & Science University, told
parents to “proceed with caution and proceed thoughtfully” if they
choose deferiprone. She added that she was not trying to dissuade
patients from enrolling but encouraged them to consider all of the
information. In
the case of NBIA, “we don’t know …if iron is causing the
problem,” Hogarth said. “Deferiprone may treat it, but it doesn’t
cure it.” She
agreed, however, that more research is needed for what some consider a
potentially promising treatment for NBIA. And if patients are going to
try it, they might want to consider doing it under the care of Vichinsky,
she said. “The way they are going about it is exactly the way it needs
to be done – thoughtfully, carefully, dealing with the bloody FDA, the
way the FDA likes to be treated, and very carefully assessing the
outcomes,” Hogarth said. Dr.
Susan Hayflick, NBIA’s premier researcher in Oregon is involved with
the trial and has a close partnership with Vichinsky. “This
is hope for a tragic, hopeless disease,” Vichinsky said, “If
deferiprone can get enough iron out of the brain, we believe it can
reverse a significant part of the disease.” If
positive results from the study are found, then all patients
participating in the clinical trial will be eligible to receive
deferiprone from ApoPharma afterward. Even if the trial is successful,
it still would take several years for the drug to go through the FDA’s
approval process and become widely available to those who do not
participate in the clinical trial. Based on preliminary enrollment criteria, deferiprone study participants must:
To
find out more about applying to take part in the study |
|
|
|
June/July 2010 The
compound pantethine shows promise as possible future treatment for NBIA With the help of
a 2008 grant from the NBIA Disorders Association, my research group
collaborated with the group of Dr. Susan Hayflick in Oregon to see
whether the compound pantethine could be a treatment for PKAN, a form of
NBIA. We
were encouraged by what we found in our investigation using fruitflies,
although more research is needed before we could test this potential in
humans. We
previously demonstrated that the fruitfly (Drosophila) model for PKAN
could be used to better understand PKAN at the cellular level. As
many of you know, the use of fruitflies to understand diseases is not
unique for PKAN and they are currently being used for other
neurodegenerative diseases such as Parkinson’s and Huntington’s. The
PKAN fruitflies carry a mutation in the Drosophila pantothenate kinase
gene, and like in humans, that gene encodes for an enzyme that is
required for the synthesis of Coenzyme A. The enzyme is critical to
metabolism and is required to convert vitamin B5 into Coenzyme A in
humans and in fruitflies. The
mutant flies show neurodegeneration, have impaired locomotor function
and have a short life span. PKAN fruitflies also show abnormalities in
specific cellular structures called “mitochondria.” Fruitfly
models are also useful to test whether compounds have some rescuing
potential for specific diseases. My group had preliminary data
indicating that the pantethine compound had a protective effect on the
PKAN fruitflies. So,
with the NBIA grant, we looked further at the rescuing potential of
pantethine. First we showed that Coenzyme A levels in PKAN fruitflies
were extremely low. Next we showed that levels of Coenzyme A increased
when pantethine was added to the food of the PKAN fruitflies.
Restoration of Coenzyme A coincided with rescue of the mitochondria,
slowed neurodegeneration and increased locomotor function. It also
extended the life span of the fruitflies. These results show that in
fruitflies pantethine can serve as an alternative source to generate
Coenzyme A when the pantothenate kinase enzyme is defective. Our
research also showed that impaired function of pantothenate kinase 2 in
specific human cultured cells also resulted in abnormalities of the
mitochondria. These abnormalities were rescued when pantethine was added
to the medium. With
these promising results, there is a suggestion that pantethine may serve
as a basis to develop a therapy for PKAN. Although a limited amount of
clinical studies in which pantethine was used to treat patients with
hyperlipoproteinemia have been done by other groups, further research is
required because pantethine is not a Food and Drug
Administration-approved drug and its effects in humans are not yet
clear. Currently,
more studies are being performed in various human cell lines and in mice
on pantethine’s potential for treating PKAN, and our group’s work in
this area will continue. |
|
|
|
March
2010
In 2007 Prof. Dr. Lars Timmerman and Dr. Amande Pauls received a seed grant from our sister organization in Germany, Hoffnungsbaum
e.V., funding a retrospective study looking at NBIA patients who underwent DBS around the world, and were able to show that DBS on average improves dystonia in NBIA patients. The retrospective study was recently published in BRAIN, a top ranking international journal in clinical neurology. A free download of the paper is available at
http://brain.oxfordjournals.org/cgi/content/full/awq022v1. |
|
|
|
February/March 2010
Two
research grants awarded with help from sister organization in Italy The
NBIA Disorders Association hoped to award two research grants this year,
but by year’s end, the board didn’t have enough money in its coffers
for more than one grant. Much of the donations raised last year under
the board’s direction went to a successful fundraising effort to try
and save the lab of Dr. Susan Hayflick in Oregon. But
then the board wondered: Could one of its two sister organizations in
Europe support a second grant? Italy said yes. With
that crucial support, the board approved two $30,000 research grants for
the 2009 grant cycle. The awards will go to Dr. Michael Kruer of the
Hayflick Lab at Oregon Health & Science University in Portland, and
Professor Dr. Lars Timmerman and Dr. Amande Pauls from the University of
Cologne in Cologne, Germany. The
awards bring to 15 the grants our organization has funded in the past
eight years. They total $450,000, almost all of them thanks to family
fundraisers and individual donations. The Associazione Italiana Sindrome
Neurodegenerativo Da Accumulo Di Ferro (AISNAF) provided funding for the
Kruer grant. Italian
families affected by NBIA founded AISNAF in 2006. Their president, Dr.
Natale Scalise, attended our 2009 Family Conference in Indianapolis and
participated in meetings with researchers there. Since then, we have had
conference calls with AISNAF and our other sister organization,
Hoffnungsbaum e.V. in Germany, focused on collaborating to promote NBIA
research. Hoffnungsbaum
e.V. sent money in 2004 to help fund a research grant and has been a
great partner. We are very happy to be working with both of these
international lay advocacy organizations and plan future collaborations
with them to keep NBIA research going. Kruer’s
grant is titled “SNP
microarray-based disease gene discovery in idiopathic neurodegeneration
with brain iron accumulation.” It
will help find gene mutations that cause some forms of idiopathic NBIA,
the name used when the genetic origin of the disorder is not yet known.
Many NBIA patients do not have identifiable mutations in either the PANK2
gene that causes pantothenate kinase-associated neurodegeneration
(PKAN), or the PLA2G6 gene, responsible for infantile
neuroaxonal dystrophy (INAD) and atypical neuroaxonal dystrophy (NAD). Idiopathic
NBIA patients, nevertheless, often have disabling movement disorders,
cognitive symptoms, and MRI findings consistent with NBIA. Without
knowing what causes NBIA in this group of patients, it is exceedingly
difficult to confirm the diagnosis, foresee upcoming challenges, or
develop effective treatments. Kruer’s project aims to fill this
crucial gap. With improved understanding of this subtype of NBIA will
come new insights into NBIA biology and treatments. The
lab will study
the genes of certain families, and once researchers have narrowed their
search to a critical stretch of a single chromosome where the
responsible gene resides, they will perform DNA sequencing to identify
it. Then, after a new gene has been identified in a single family, the
researchers can sequence it in other patients with idiopathic NBIA to
determine if they, too, harbor mutations. This approach has already been
used to identify a new NBIA gene discovered at the OHSU lab that will be
published shortly. The data suggests that several additional genes await
discovery. If you or your child has idiopathic NBIA and wish to be
included in the search for a causative gene, please contact Dr. Kruer
through Allison Gregory, M.S. at gregorya@ohsu.edu. “We
are extremely grateful to the NBIA Disorders Association and AISNAF for
supporting this project,” Kruer said. “It comes at an exciting time
for NBIA research, but at a time when funding is extremely difficult to
come by. With the momentum we have established already and with the
generous support of the family organizations, we believe that our work
will transform ‘idiopathic NBIA’ into recognized subtypes of the
disease, a crucial step in characterizing and then developing effective
treatments for NBIA.” Timmerman
and Pauls will be working on a grant titled “Stimulation
of the Globus pallidus internus in patients with NBIA (formerly
Hallervorden-Spatz-Syndrome): prospective analysis of international
therapeutic outcomes and development of a therapeutic algorithm.” This
will be a prospective, open trial, multi-centre study that will look at
outcomes of deep brain stimulation (DBS) in patients with NBIA. DBS is
used to help alleviate severe dystonia, a painful condition common in
NBIA patients. Dystonia
is a term used to describe slow, involuntary, and sometimes winding
movements of the limbs and trunk, occurring at rest and during action.
The movements frequently are worsened by voluntary movement. Dystonia
generally is treated with oral medication, botulinum toxin and deep
brain stimulation (DBS). Oral medication helps some patients, but is
frequently insufficient for severe dystonia. Botulinum toxin is very
good for localized, focal problems such as neck posturing or pointing of
toes, but cannot easily be applied to the whole body. DBS is sometimes
used when dystonia affects the whole body, and studies have shown it to
be effective for other conditions causing dystonia. In
2007 Timmerman and Pauls received a seed grant from our sister
organization in Germany, Hoffnungsbaum e.V., funding a retrospective
study looking at NBIA patients who underwent DBS around the world, and
were able to show that DBS on average improves dystonia in NBIA
patients. However, this study was limited in predicting which patients
would benefit most from DBS surgery and which would not. The
retrospective study was recently published in BRAIN, a top ranking
international journal in clinical neurology. A free download of the
paper is available at http://brain.oxfordjournals.org/cgi/content/full/awq022v1. With
the future prospective trial, Timmerman and Pauls hope to gain more
insight into which NBIA individuals benefit from DBS. They will collect
data on patients before they undergo DBS and follow them over two years.
They also will collect information on the severity of the patient’s
dystonia, other medical problems, supportive therapy (such as
physiotherapy, feeding tube, etc.), degree of disability, activities of
daily life and quality of life. With the study they are looking for
answers to the following questions:
They hope to pool data from both studies to increase their chances of being able to find predictors of therapeutic outcome. Thus, if you or your child has decided to undergo DBS as a treatment for NBIA dystonia, please contact amande.pauls@uk-koeln.de so you can take part in the study and help other patients, parents and doctors. |
|
|
|
February/March
2009
Two
more applicants win NBIA grants A
well-known NBIA researcher in the United States and a scientist from the
Netherlands each received $30,000 awards from the NBIA Disorders
Association to advance research into these disorders. The
seed money brings to 13 the number of grants awarded by the board in the
past seven years, for a total of $390,000. The grants are the direct
result of family fundraisers held in communities across the United
States, as well as private donations. The
board chose to seed projects submitted by Dr. Susan Hayflick of Oregon
Health & Science University and Dr. Ody Sibon of the University
Medical Center Groningen in The Netherlands. Hayflick
and her laboratory won for a project entitled “Proteomic Analysis of
Neuroaxonal Spheroids.” Although it has been known for some time that
axonal spheroids are seen across the various forms of NBIA, little is
known about how they occur or what is inside of these formations. The
axon is the long, projecting portion of a nerve cell that transmits the
nerve’s message to another location. Spheroids appear under the
microscope as abnormally bloated, swollen areas in the axon. Through
using new techniques to capture and dissect spheroids, the Hayflick lab
will analyze the types of proteins found inside them with the intent of
learning more about the process leading to their development. Spheroids
from animal model tissue, as well as human tissue from individuals who
had PKAN, INAD, atypical NAD and other NBIA disorders will be studied. “After
we compare the proteins in the spheroids from different animal models
and patient tissues, we may find the common components and associated
signaling pathway underlying the axonal spheroid formation, which will
serve as a target for drug development and disease treatment in the
future,” said
Dr. Wei-hong Xiong, who will focus most of his time on this project. Sibon’s
grant is titled “Investigating the Potential of Compounds to Rescue
Pantothenate Kinase Deficiency.” The Sibon lab recently established a
Drosophila (fruit fly) model for Panthothenate Kinase-Associated
Neurodegeneratoin (PKAN), one of the disorders under the NBIA umbrella. PKAN
is caused by defects in the pantothenate kinase 2 (PANK2) gene.
The Drosophilia PKAN model can now be used to obtain fundamental insight
into PKAN pathogenesis and can also be used to identify compounds that
are able to rescue disease-associated characteristics. Pantothenate
kinase is the first enzyme required for the pathway leading to the
biosynthesis of Coenzyme A. This pathway and the genes coding for the
enzymes involved are highly conserved throughout evolution. The
Drosophila has one PANK gene and it is similar to PANK2 in
mice and humans. Drosophila that carry mutations in the PANK gene
show characteristics such as neurodegeneration and a decreased life
span. While
Drosophila only has one PANK gene and humans and mice have four, the
presence of one PANK gene simplifies the fundamental research to
understand what the consequences are of disrupted pantothenate kinase
activity and simplifies screens for compounds able to protect against
PKAN disease characteristics. Recently
in the Sibon laboratory a protective compound was identified that slows
down the neurodegeneration and increases the life span in the Drosophila
PKAN model. With the grant award, and in collaboration with the Hayflick
laboratory, the mode of action of this compound will be further tested.
Researchers also will try to learn whether this compound provides
protection in affected tissues of Pank2 knock-out mice. |
|
|
|
October 2008
NBIA
Disorders Association Scientific and Medical Advisory Board (SMAB) |
|
|
|
December
2007
Board awards three $30,000 grants to study NBIA in 2007 grant cycle |
|
|
|
August
2007
NBIA research
sparks links to other labs, better known diseases The discovery of a
second NBIA-related gene in 2006 has opened up new collaborations and
new research frontiers, scientists reported at the Fourth International
Family Conference in Cincinnati, Ohio. Fundraising by
families continues to play a key role in ongoing research and provided
crucial seed money that led to the latest gene discovery, said Dr. Susan
Hayflick of the Oregon Health & Science University. “It reminds us of
why we come to work everyday,” Hayflick told about 80 conference
participants who gathered from around the world in early May. “We are
trying to beat this thing.” A clinical test is
now available at the OHSU DNA Diagnostic Lab to
help families determine their chances of passing NBIA to their children
if they have the second gene, known as PLA2G6. Hayflick’s lab
worked with researchers from the University of
Birmingham School of Medicine in the United Kingdom and from the
University of California San Francisco to identify the gene, and those
scientists continue to collaborate on research now underway. Mouse
studies are helping to reveal the NBIA disease process and will also be
used to test new therapies. In one area of research, UCSF scientists
removed B5 from the diet of healthy mice and the animals developed
dystonia, a common symptom of NBIA, Hayflick said. Dr.
Paul Kotzbauer, a neurologist and researcher at Washington University in
St. Louis, and Lars Timmermann at University Hospital in Cologne,
Germany, also are among those collaborating on NBIA research. Kotzbauer has
been studying mice with mutations in the PLA2G6 gene to examine
changes in brain function that may be similar to those that occur in
NBIA patients. He also noted that the same Lewy bodies – fibrous
protein deposits in nerve cells – that are seen in the brains of
Parkinson’s patients also can be found in NBIA patients. The
connections between NBIA and Parkinson’s as well as Alzheimer’s
disease have become more apparent since the discovery of the PLA2G6
gene. “I
can argue in grant applications to the NIH,” Kotzbauer said, referring
to the National Institutes of Health, that NBIA “is important to
study…because what we learn can be important for Parkinson’s disease
and Alzheimer’s disease.” Pointing
out such links can be increasingly important because money from the NIH,
the federal agency that funds much of the nation’s medical research,
is declining, Hayflick said. Timmermann
is studying Deep Brain Stimulation and wants to learn more about how
effective it is for NBIA patients. The data, while promising, is sparse. Timmermann
is seeking participants for a study so that he can follow patients
having the procedure and see how they fare a year or longer after the
procedure, he said. Such data could help parents and NBIA individuals
make more informed decisions about whether to seek the procedure. (See
article on DBS, page XX.) All
of the research costs money, and the NBIA Disorders Association has
provided eight $30,000 grants since 2003 and expects to award one or
more this year, thanks to member-sponsored events. Without the seed money from family fund fundraisers and other NBIA member-sponsored events, Hayflick said her lab might not have been considered for additional federal grants needed to move her work forward. NIH grants are more competitive than they ever have been in her career, she said, and she is convinced: there are more NBIA-related genes waiting to be discovered. |
|
|
|
August
2007
Family
conference provides shot in arm to NBIA’s BioBank for scientific
research A
two-day marathon of blood giving during the Fourth International
Family Conference in Cincinnati provided the first opportunity to
collect samples for the NBIA Disorders Association’s BioBank in the
United States. The
collections follow a similar activity by our sister group in Germany,
which obtained 22 samples from nine NBIA families at its third Family
Conference in November. The combined efforts bring the samples in our
BioBank to 101, representing 33 NBIA families. These families come from
all over the world, including Canada, England, France, Germany, Iceland,
India and the United States. Although
many families have donated blood in previous years, the new samples were
necessary because the prior ones went to the registry at Oregon Health
& Science University. They have been depleted by research. Faced
with the choice of sending a miniscule amount of blood to the BioBank,
the NBIA Disorders Association chose to collect new samples. It wants
all NBIA affected individuals and immediate family members to donate to
the BioBank, created by the Genetic Alliance, an umbrella organization
for groups representing rare diseases. The
NBIA Disorders Association is a founding member of the Genetic Alliance
BioBank, which provides storage facilities and support to organizations
like ours. The NBIA Disorders Association’s BioBank collects, stores, processes and distributes biological
samples to aid in research. The BioBank has the potential of collecting
and storing many types of samples, such as blood, tissue, cells and DNA,
from NBIA-affected individuals and their immediate relatives. These
biological samples, along with medical information from individuals with
NBIA and their relatives, are essential for studying NBIA. The samples
and information can be used to help researchers find other gene
mutations responsible for NBIA and conduct research that will explore
the causes of and potential treatments for NBIA. Researchers
interested in studying the samples submit proposals to
the NBIA Disorders Association’s Scientific and Medical Advisory
Board. That board reviews the proposals and determines which ones merit
approval. At
the association’s Cincinnati conference, collecting the samples was a
remarkable endeavor on the part of many people. Thanks to the families
who meticulously completed the many consent documents and clinical
history forms. Their cooperation is greatly appreciated On
a personal note, it was a pleasure to finally meet all of the families
with whom I corresponded before the conference. Fellow board member
Susan Laupola coordinated the efforts of the phlebotomists; she and her
staff were extraordinary and deserve much credit for their expertise. |
|
|
|
August
2007
Have you or your child had DBS? Thinking about DBS for the future? Dr. Lars Timmermann, director of the Movement Disorders and DBS program at University Hospital in Cologne, Germany, is now actively enrolling NBIA patients with DBS and those planning to have DBS surgery in a new research study. The goal of this important study is to create an international database of NBIA patients with DBS so that their progress can be followed and outcomes measured. This will help show whether DBS helps people with NBIA, how it can best be done, and the most effective settings for the DBS stimulator. If you are interested in this study, please contact Dr. Timmermann or his collaborating PhD student, Karolin Wieland, at: karolin.wieland@smail.uni-koeln.de or lars.timmermann@uk-koeln.de. |
|
|
|
Research
Update |
|
April 2007 NBIA
board now accepting research grant applications Once
again, the NBIA Disorders Association board is accepting applications
for one-year research grants from scientists interested in studying
NBIA. That work can involve the early detection, diagnosis or treatment
of patients with NBIA. Applications are available at our Web site at
www.NBIAdisorders.org. These
are $30,000 seed grants to conduct small clinical studies, the results
of which can be used to obtain funding for larger studies from a
corporate sponsor or a federal agency such as the National Institutes of
Health or Food and Drug Administration. The
NBIA board hopes to award two or three research grants this year, thanks
to vigorous fundraising by families in 2006. Researchers
are asked to submit letters of intent no later than June 15. Full
proposal invitations are due July 31 with a deadline for submission of
Oct. 1. Award announcements will be made in November with funding to
begin in December. |
|
|
|
April
2007
Deep brain stimulation providing hope to NBIA
patients worldwide He
was 14, cheerful and in terrible pain. He suffered from severe dystonia
— a movement disorder that causes muscle tightening, limb twisting and
painful postures. This young man's problem was so bad he could not
perform the most mundane daily activities. He
was suffering from the PKAN-form of NBIA, and his family asked me, a
neurologist and movement disorder specialist, to help. My team and his
parents were considering all options to alleviate his distress. Traditionally,
generalized dystonia in NBIA patients is treated with high doses of
medications like tri-hexiphenidyl, benzodiazepine or baclofen. However,
powerful doses of those medications are often accompanied by strong side
effects. A great alternative is Botulinum Toxin, a poison that can be
locally injected for a temporary release of the abnormal muscle tension.
Even still, the dose cannot exceed a certain limit. Therefore, Botox
cannot help in all body parts of a patient with generalized dystonia. A
new option for these patients is deep brain stimulation, or DBS. It
affects the internal globus pallidus. The idea is that abnormal neuronal
activity in parts of the brain can be "blocked" by a
high-frequency electrical stimulation. To establish such an
"electrical blockade" a specialized team of neurosurgeons,
neurologists and anesthesiologists implant fine electrodes with
submillimeter accuracy in specific target regions of the brain. DBS
in generalized dystonia was described as a highly effective treatment in
previous studies. Using it as a therapy for dystonia patients with NBIA
has been shown in a few single case reports as well as in a small series
of patients. Dr.
Pierre Castelnau from France published in 2005 a study of six patients
with PKAN treated with DBS. The authors could demonstrate in four
patients with the classic form of the disease and two patients with the
atypical form of the disease a dramatic reduction of dystonia with DBS. Deep
brain stimulation is an invasive therapy with the minimal potential of
lethal complications. It is therefore even more necessary to broaden the
knowledge about this potentially highly effective therapy. Because NBIA
is a rare disorder, an analysis of the treatment results will always on
one hand have the burden of small numbers of patients, and on the other
hand lead to different treatment approaches around the world.
Consequently, a detailed international analysis of results is even more
important to answer clinical questions based on evidence-based data.
Decisions of patients, relatives and clinicians about invasive
therapeutic procedures have to be based on the best information we can
provide. From our point of view, a series of urgent questions regarding DBS in NBIA patients need to be answered:
We
have designed a new study and are asking NBIA patients to help us answer
these important questions. It has been approved by the ethics committee
of the University Hospital Düsseldorf (International Master Votum) and
is designed in accordance with the strict German Data Protection Act.
With the support of the NBIA Disorders Association and Hoffnungsbaum e.V.
(Germany) we intend to contact all worldwide DBS centers who have
experience with DBS in NBIA patients. We
will request information and data from the treating physicians, patients
and relatives, including MRI findings, dystonia rating scales, target
point, stimulation parameters, as well as information about quality of
life before and after the operation. Data will be pooled and
statistically analysed by an independent institution, with financing
established by the German Hoffnungsbaum e.V., the sister organization of
the NBIA Disorders Association in the United States. Results of the
study and a "standardized treatment plan" will be published
together as an international multi-center cooperation paper including
all participating physicians as well as an international supervising
board of DBS experts. A
few weeks ago I saw my young patient with NBIA again. After trying all
other treatment options he, his family and our team decided to try DBS.
It was a long journey of treatment, rehabilitation and adaptation of the
stimulation. To my delight, his posture is remarkably improved, his hand
function is much better and his overall functioning in every day life
considerably better. If you or your child has been treated by DBS and you are interested in participating in this international project we would be happy if you or your doctor would contact us via email: lars.timmermann@uk-koeln.de or timmermann@neurologie.uni-duesseldorf.de. Please don't hesitate to contact our group if you are just considering or planning DBS. We are happy to answer any questions you may have on this topic. |
|
|
|
December
2006
NBIA
board awards new research grant to study patients with two NBIA genes Fundraisers
by NBIA families have paid off, enabling the NBIA Disorders Association
board to award another $30,000 research grant. It will go to Dr. Susan
Hayflick’s lab at the Oregon Health & Science University and is
the fifth such grant her lab has received among eight the board has
awarded in five years. Hayflick’s
latest project will look at molecular changes in cells of patients with
two genetic forms of NBIA. The genes involved are PANK2 and PLA2G6.
By identifying cellular changes that are common to both forms of NBIA,
her lab expects to generate new understanding of the disease process and
also identify promising new targets for therapies. Research
support from the NBIA Disorders Association continues to be a critical
resource to enable investigators to generate preliminary results so they
can compete for funding from the National Institutes of Health to carry
the research further. In the past, $30,000 of seed funding has blossomed
into $1million in federal grant support. The NBIA board considers that a
good return on its investment. This
is the first time the organization has used its Scientific & Medical
Advisory Board to review grants and advise the Board of Trustees, which
has the final say on grant awards. Before, the National Organization for
Rare Disorders evaluated the grant proposals and recommended awards, for
a fee of $5,000 per grant. Dr.
Hayflick serves on NBIA’s SMAB and recused herself from the review
process to avoid a conflict of interest. |
|
|
|
August
2006 New gene found! by Patricia Wood An international
team of geneticists, led by Dr. Susan Hayflick of Oregon Health &
Science University and Dr. Eamonn Maher of the University of Birmingham
in Manchester UK, discovered a new gene that causes NBIA. The finding,
which is the second NBIA gene to be discovered, is significant because
it will accelerate research into the disease and help scientists in
their quest for a cure. The first gene, PANK2,
believed to cause about half of NBIA cases, was discovered in 2001 by
the laboratory of Dr. Jane Gitschier at the University of California,
San Francisco in collaboration with the lab of Dr. Hayflick. It has long been
thought there was an association between INAD, also known as
Seitelberger disease, and NBIA. This new gene discovery confirms that,
although there is still much to be learned about how this gene causes
disease. Two seed grants
from NBIA Disorders Association through the National Organization for
Rare Disorders were used to help in the search for this gene. One was to
Dr. Natalie Canham of the University of Birmingham in England in
September 2003 and one was to Dr. Hayflick in 2004. It became an
international effort with many groups participating and is a great
example of how NBIA families and the association's research grants can
make a difference and indeed already have! We asked Allison
Gregory, a genetic counselor at Oregon Health & Science University,
about the discovery. Q: What is
the new NBIA gene? Q: What is
INAD? INAD usually
develops during very early childhood, causing loss of early milestones.
Affected children eventually lose their ability to move or speak.
Common features of INAD include optic atrophy and incomplete development
of a brain structure called the cerebellum. Like PKAN and other
forms of NBIA, INAD is inherited in a recessive fashion. This
means both parents are carriers and an affected individual has no
working copy of the gene. Q: Is INAD a form
of NBIA? Q: Why is the
gene named PLA2G6? Q: How does
this gene cause the disease? Q: How was
the gene discovered? Once our labs
identified this region, OHSU worked on one half while our collaborators,
Drs. Eamonn Maher and Neil Morgan at the University of Birmingham in
England took the other half. This was very detailed work that involved
searching through each gene systematically to find changes in the code
that could cause the disease. It took many months of searching
before the lab in England finally found the first changes in PLA2G6.
We were quickly able to verify gene mutations in many of the INAD
families that we had collected in our lab. Q: Is there a
blood test for this gene? Is prenatal diagnosis possible? Once it is
available, the test should take about three weeks to complete and will
require a blood sample. For families in which the mutations can be
identified in the affected child, prenatal diagnosis will be an option
for any future pregnancies. Our recent studies
have taught us that people who were diagnosed with NBIA (not INAD) can
also have mutations in PLA2G6. For this reason, people with
NBIA who have tested negative for the PANK2 gene should ask
their doctors about testing. Based on what we know now, it is
likely that some people from this group will have changes in this gene.
Q: Why is the
discovery of this gene important for the entire NBIA community? The new gene
discovery also gives scientists a new target for developing NBIA
therapies. Up till now, ideas for therapies have been focused on
pantothenate, coenzyme A and iron. PLA2G6 functions differently from
PANK2 in membrane repair. As we better understand its precise role in
this process, new ideas for therapies will come. We don't have a
cure yet for any of the NBIA disorders, but now is a good time to
reflect on how far we have come in the past 5 years. Two major NBIA
genes have been identified. An increasing number of scientists from
around the world are working to advance understanding of the NBIA
disorders. New symptomatic treatments have become available (e.g. deep
brain stimulation). And the NBIA Disorders Association is gaining in
strength (new research programs) and numbers (new members and
affiliates). Our model of families working in close partnership with the
research community is at the core of these successes. |
|
|
|
August 2006 Board could award two $30,000 grants this year The NBIA Disorders
Association board has enough money in its research kitty this year to award two
$30,000 seed grants, thanks to fundraisers by families. These grants are a
significant part of the association's mission. They encourage important clinical
studies designed to improve the diagnosis and treatment of Neurodegeneration
with Brain Iron Accumulation. They can also be used to attract additional
research money to further the scientific work from corporate sponsors or other
agencies, including the National Institutes of Health and the Food and Drug
Administration. The grant process for this
year is well underway. The NBIA Scientific & Medical Advisory Board is now
reviewing letters of intent from researchers and will soon determine whom to ask
to submit full proposals. The deadline for full
proposals is Sept. 30. The advisory board will review them and make
recommendations to the NBIA board of trustees, which have the final say in grant
selection. Awards are to be made by
Nov. 15. If no proposal meets the board's requirements, monies will be held over
until next year when the process starts again for grants in 2007. |
|
|
|
August 2006
New board member will coordinate collection of DNA BioBank samples With the addition of a new board member, the NBIA Disorders Association will launch a new effort to encourage families to donate blood samples to our BioBank. We are grateful to families who have sent in the paperwork to release DNA samples and medical records from the Research Registry housed at Oregon Health & Science University. And we appreciate any who have requested consent forms, agreeing to send samples directly to our BioBank. We apologize that we have not, until now, had someone on board to expedite this process. But new board member Matthew Hodgson, who joined in May, is now ready to coordinate this effort and will be in touch with families who have responded to our request for samples and others who have not yet been in touch. We will be transferring these samples from Oregon to the BioBank in the fall. So please be sure and send in your form as soon as possible to help us save costs and to participate in this important endeavor. |
|
|
|
April
2006 Fundraisers
make a big difference. Because
families held several last year — and we hope more of them will step
up with fundraisers this year, the NBIA Disorders Association will be
able to offer at least one research grant worth $30,000 in 2006. Our
organization has used the National Organization for Rare Disorders to
administer seven research grants that we awarded in the past four years.
But we have evolved. Thanks to our new Scientific & Medical Advisory
Board, we now have the in-house expertise to do the work ourselves,
saving $5,000 in administrative costs per grant. The advisory board will
review proposals and make recommendations to the Board of Trustees,
which will have final say in grant selection. Any
advisory board members wishing to apply for grants will recuse
themselves from the selection process to avoid conflicts of interest. We
are accepting applications for one-year grants for clinical research
studies related to the early detection, diagnosis or treatment of
patients with NBIA. The application and instructions can be found at our
Web site at www.NBIAdisorders.org under the RFP link on our home page.
The deadline for letters of intent is June
15, 2006. The grant will be awarded in November. The
purpose of these grants is to encourage meritorious clinical studies
designed to improve the diagnosis or therapy of Neurodegeneration with
Brain Iron Accumulation. The research will be conducted in the United
States, Europe, Canada, Australia, New Zealand, Brazil, Argentina,
Chile, South Africa, Japan, or Israel, and where supervision of grant
administration is possible. Grants
will be awarded to academic researchers to initiate small clinical
trials, the results of which could be used to obtain funding from NIH,
FDA or other funding agencies, or to attract a corporate sponsor.
Procedures or proposed therapeutic trials may be new, based on recent
biochemical or pharmacological evidence, or be in preliminary states of
clinical investigation. Evaluation
of proposals will include careful consideration of protocol design,
objectiveness of parameters measured, and statistical evaluation
proposed. Protocols that will focus on early detection, diagnosis, or
treatment (Pharmacological, devices, surgery or dietary) will be given
priority. For
more information, contact Patricia Wood at pwood@NBIAdisorders.org. |
|
|
|
April
2006 Please don’t ignore recent letters about BioBank, even if you donated previously By Patricia Wood Did
you get your letter yet? The
NBIA Disorders Association mailed letters the first week of March
telling families about our BioBank and why we need their help with this
important endeavor — even families who have already donated blood. For
previous donors, a few signed forms are all we need. Specifically,
we are requesting that families who have previously donated blood
samples for the NBIA Research Registry housed at Oregon Health &
Science University send in the release forms to our office that were
included in the packet. This
release asks OHSU to send a sample of the DNA and the medical records of
NBIA individuals to our BioBank. We need a separate release form for
each individual who donated blood. OHSU
will still have DNA available for its research, but these samples will
now also be available to other researchers who wish to study NBIA. Instructions
for those who haven’t donated blood also are in the packet, and we are
urging families to take part in the BioBank. Our
membership in the BioBank greatly increases the odds of encouraging new
researchers to study NBIA. All researchers desiring samples and data
must have their projects approved by the association’s Scientific
& Medical Advisory Board to make sure their research is an
appropriate use of our valuable resources. Researchers will also have to
report back to us on their findings and we will then inform everyone on
their progress through our Web site and newsletters. The
BioBank eliminates families having to donate blood multiple times for
different research projects. It also protects the privacy of those
donating. Names and identifying information will be removed and
researchers will not have access, but will have anonymous data. Our
organization will also be able to gather information from families over
a period of years, giving a clearer picture of how the disease
progresses. As
many of you know, this is crucial information in working toward a cure
for NBIA. So, if you have
donated blood previously to OHSU, please send in your release forms as
soon as possible. If you are a newly diagnosed family or have not yet
donated blood to OHSU for other reasons, you can fill out the request
for consent forms and we will send you the necessary paperwork to
participate. Please contact me, Patricia Wood, at pwood@NBIAdisorders.org
or call 619 588-2315 if you have any questions. Any
NBIA families not receiving the packet should also contact me to make
sure we have your correct address and that you are listed in our NBIA
families database. We
are very excited to be moving forward with our BioBank. As one of seven
founding members of the Genetic Alliance BioBank, we envisioned this
repository moving research forward at a faster pace. Our participation
was possible with a $50,000 grant from the Wright Family Foundation. One
of our other founding groups, CFC International that is also a small,
rare disease group, recently made news with the discovery of three genes
related to their disease. This research was possible only because the
organization had DNA and medical records available to a researcher that
otherwise would have had no access to this material. It took only a few
months for her lab to discover these genes, but it would never have
happened without CFC International’s participation in the Genetic
Alliance BioBank. CFC International was named a co-author of the gene
discovery, only the third time that a lay advocacy group had
accomplished that feat. The
discovery may help with the study of cancer, as these three genes are
part of a complex pathway called Ras/MAPK that has a central role in
cell growth, where disruptions can lead to cancerous tumors.
As cancer is not part of CFC, this sheds new light on the complex
process of this pathway. Please do your part to help NBIA Disorders Association further critical research. Many families report feeling helpless in their fight against NBIA, but this is a way to fight back and make a difference. |
|
|
|
December
2005 Dr.
Susan Hayflick’s lab at the Oregon Health & Science University has
been awarded the 2005 research grant from the National Organization for
Rare Disorders, sponsored by funds from NBIA Disorders Association and
Hoffnungsbaum e. V. (NBIA Germany organization). The title of the
project is “Dynamics of Brain Iron Distribution in PKAN.” Her
lab will study how iron moves into the brain of individuals who have
PKAN, a form of the disease, and in individuals who have the non-PKAN
form of NBIA.
“We were very pleased to be awarded the 2005 grant from the NBIA
Disorders Association and Hoffnungsbaum ,” Hayflick said. “Since
this is the only way for us to explore new research ideas and obtain
preliminary data for larger federal grants, these funds are extremely
valuable in supporting NBIA research.” She
is hopeful the research will lead to insights into problems of vitamin B5
metabolism and brain iron accumulation, links that still are not clear.
“We hope that by understanding these patterns we can generate new
ideas for blocking iron deposition,” Hayflick said. |
|
|
|
December 2005 The
NBIA Disorders Association will be offering at least one research grant
this year, thanks to fundraising efforts by NBIA families in 2005. There
is still time for more families to hold fundraisers so that more grants
can be offered before the awards are made at the end of the year. To
save money and to exploit the association’s growing expertise, our
Scientific and Medical Advisory Board will review grant applications and
recommend awards. In the past, the National Organization for Rare
Disorders reviewed and administered research grants at a cost of $5,000
per grant. The
NBIA board is compiling a mailing list of researchers to solicit
proposals for grants. NBIA families also are encouraged to send the
names and addresses of researchers they believe might be interested in
studying NBIA so the board can notify those prospects of the program.
This contact information should be sent to board member Kris McGourthy
at rural9@aol.com. After
receiving letters of intent, our Scientific & Medical Advisory Board
will decide who will be asked to submit full proposals to be reviewed
and scored. That board will then make recommendations to the NBIA
Disorders Association Board, which has the final say on funding
proposals. |
|
|
|
December 2005 Our
daughter Kelsey didn’t stop giving when she passed away. In life
Kelsey brought smiles to the faces of those she loved, and now, with her
passing, Kelsey is giving the gift of hope to people who have NBIA and
their loved ones. With
the gift of Kelsey’s brain tissue, researchers now have the means to
explore a central mystery of NBIA, the ‘eye of the tiger,’ a key
feature of the disease. It is an area in the brain encased in a layer of
iron that distorts the view of the brain that can be seen by Magnetic
Resonance Imaging. This distortion prevents the MRI from detecting the
mass held within the iron cell, the contents of which doctors say are
primary to the cause of NBIA. Donations
such as Kelsey’s help doctors gain a crucial piece to the puzzle of
NBIA. The end of the marathon race for a cure is in sight, but without a
strong finish, without continued funding and without continued research
and donations of tissue, the first 23 miles will have been run for
nothing. History has shown us that nothing is impossible, that no
disease is incurable. What started as an uphill battle against the odds
is close to victory. All the pieces now lay before us; we just have to
put them together. When
Kelsey was diagnosed with NBIA little was known about the disease aside
from the eventual and inevitable outcome: death. Kelsey’s battle with
NBIA, we were told, would not simply be a difficult one, but a futile
one. Doctors tirelessly searched for a cure, but ultimately were stuck
trying to complete a puzzle without all the pieces. Kelsey’s parting
gift provides a crucial piece to that puzzle – and hope it will be
solved. If you would like to make a designation for a future brain tissue donation, please contact info@NBIAdisorders.org for more information. |
|
|
|
April 2005 PKAN Knock-out Mice created and studied at UCSF By Allison Gregory The NBIA research teams at UCSF and
OHSU recently published an article in the journal Human Molecular
Genetics describing the creation and analysis of a PKAN knock-out mouse.
Knock-out mice are animals that have had a certain gene
inactivated, or “knocked out.”
In this case, the Pank2 (the mouse gene is referred to in lower case letters, while
the human PANK2 gene is written in all capitals) gene was knocked
out, which resulted in a mouse version of classic PKAN. Knock-out mice can be extremely
helpful to researchers by giving clues about the underlying causes of
diseases. They also provide
an initial way to test possible treatments.
Since mice reproduce relatively rapidly (a female mouse is
pregnant for only about 20 days before giving birth to a litter of
pups), it is possible to design different crosses of mice and collect
several generations over a short period of time. How to make a knock-out mouse Several advances in technology have
made what was previously a stupendous feat a common research tool.
The first step is to knock out the gene in a group of mouse
embryonic stem cells. Only
one of the two copies of the Pank2
gene is knocked out at this point, leaving the second working copy. Once the gene has been knocked out,
the stem cells are injected into very young mouse embryos created by in
vitro fertilization techniques. At
this early stage, some of the new cells are incorporated into all the
different organs of the developing mice, including the cells that will
become sperm and eggs. These embryos are then transferred back into
surrogate mouse mothers. About
16 days later, a litter of pups is born. The pups have a mix of normal cells and knock-out cells. Some pups will have the knock-out
gene incorporated in their sperm and egg cells.
They are mated and pass on this trait to some of their pups.
The pups have the new change in every cell of their bodies and
are PKAN carriers. Then,
carrier mice are mated to create the true knock-out mouse, which has
mutations in both copies of its Pank2
gene. After three generations of mice and much hard work, several
male and female knock-out
mice are available to study. Studies of the PKAN knock-out mice Several aspects of the mouse’s
development, health, and physical skills were studied.
They were always compared to healthy carrier mice (one working
copy of Pank2) and healthy
normal mice with two working copies of the Pank2 gene. The mice were monitored for feeding
difficulties and poor growth because these are problems seen in people
with PKAN. The knock-out
mice were smaller in size and body weight--about 80% the size of the
control mice. However, they
ate the same amount as the normal mice and did not appear to have
trouble with chewing or swallowing.
This suggests that there are probably differences in their
metabolism that make them smaller. Fertility was studied in male and
female Pank2 mice.
Pank2 mice cannot mate with each other. The females were found to be
fertile when mated to normal mice, but they produced much smaller
litters. The males were
found to be infertile. Although
they produced the precursors to mature sperm cells, their development
stopped prematurely and no fully developed sperm were made. Like people with PKAN, the mice had
retinal disease. This was shown by electroretinogram studies and by looking by
histology at retinal tissue in the laboratory.
As in humans, the damage to the photoreceptor cells of the retina
worsened over time. The neurological assessment of the
mice was of special interest since PKAN is primarily a neurological
disorder. The mice were
followed for over a year, which is roughly equal to 34 human years (lab
mice usually live about two years).
Surprisingly, no evidence of iron accumulation was seen in the
basal ganglia and the mice did not have any noticeable neurological
impairments. Their brains
were evaluated both by magnetic resonance imaging (MRI) and by studying
tissue samples from deceased mice.
They were given several tests weekly to measure their strength,
balance, and muscle coordination. Discussion of the research findings The researchers successfully created
a mouse that lacks pantothenate kinase 2, the enzyme that is deficient
in PKAN. In studying the
mice, they found growth problems, retinal degeneration, and absent sperm
in the males. Most surprising was the finding of
infertility in the male mice. This
has not been described in human males with PKAN, probably because many
of the affected individuals with classic PKAN have a shortened lifespan
or are very ill. A question
for future research is how the Pank2 protein is involved in the development of mature sperm cells. Although the retinal degeneration in the mice provides a model for studying this problem in people with PKAN, the mice did not have a movement disorder or show any abnormal iron accumulation in their brains. The next step is to see whether the researchers can bring out these features in the mice. They are currently experimenting with giving the mice various compounds, including a diet that is low in vitamin B5, to see how deprivation of the vitamin will affect them. |
|
|
|
December 2004 Hayflick
and her collaborators found the gene that causes pantothenate kinase-associated
neurodegeneration (PKAN) in 2001, called PANK2. About half of all people
diagnosed with neurodegeneration with brain iron accumulation (NBIA)
have mutations in the PANK2 gene. The other half has genes that remain
to be found. Even
before the recent NORD funding was awarded, Hayflick was on the trail of
the next gene. She received support last year from the NIH-funded Center
for Inherited Disease Research, or CIDR. This
center provides many critical services to researchers. For Hayflick,
CIDR took on the task of processing almost 200 DNA samples from the
international NBIA family registry that is maintained in her lab. An
individual "fingerprint" of each person's DNA was generated so
that the team could start narrowing down the location of the next NBIA
gene among the 24 unique human chromosomes. This is done by looking at
each family and checking what parts of the fingerprints are always
different between the people with NBIA and those without it. This first
step is like starting with the entire world and narrowing down the
possible location to a few countries. The
NORD funding will support the next steps. These include doing some
additional fine mapping, which narrows down the location even further.
Fine mapping is like finding cities inside the countries. Once the
location is narrowed down to a smaller region of a certain chromosome,
new techniques can be combined to find the gene as quickly as possible. Since
such great progress has been made in recent years with mapping the
entire human genome, candidate genes can now be identified within
specific 'regions of interest.' These candidate genes are screened to
see whether there are any mutations, or typos in the genetic code, that
could cause someone to have NBIA. The
identification of another major NBIA gene will be a launching pad for
progress in several areas. A molecular test could be developed to help
make the diagnosis of NBIA. This would also make prenatal diagnosis
possible for many couples concerned about the chance of having another
child with NBIA. The
research team hopes that by identifying the genetic basis of the disease
in these remaining families, progress will be made towards better
understanding the processes that cause NBIA so therapies can be
developed. This could benefit everyone with NBIA, including those with PKAN, since we may find a related gene that sheds light on pathways common to all forms of this disorder. |
|
|
|
December 2004 By Allison Gregory Dr.
Susan Hayflick and her collaborators at Oregon Health & Science
University (OHSU) have finished analyzing the ophthalmological data that
was collected during the Clinical Investigations of PKAN study. This
part of the study,
led by doctors Richard Weleber and Robert Egan of
OHSU’s Casey Eye Institute, found that 11 of 16 participants had
abnormal electroretinogram, or ERG, results.
This test measures how well the rod and cone cells in the back of
the eye are working and can detect dysfunction even before someone
notices vision changes. Four
of the 11 had true retinal disease, and their ERG findings were the most
severe. For the others, the ERG changes were mild to moderate and showed that PKAN has affected the rods and cones of their retinas, but not yet to a significant degree. Almost all the participants also had ocular motility changes, meaning they had trouble moving their eyes to track objects or do other tasks. None
had optic nerve atrophy, which confirmed the theory that this is a
feature of non-PKAN NBIA. Egan,
a neuro-ophthalmologist, also noticed some interesting similarities
between the PKAN study participants and two other patients he has seen
recently, one with non-PKAN NBIA and one with Wilson disease, a copper
storage disorder. The OHSU team will continue to keep the NBIA Disorders Association informed about the findings of the clinical PKAN study. |
|
|
|
October 2004 Genetic Alliance BioBank launched Washington
DC – October, 2004 Seven genetic advocacy organizations, including the
NBIA Disorders Association, established the Genetic Alliance BioBankTM,
a repository for the standardized collection, storage and distribution
of biological samples and clinical data for research purposes. This
novel, advocacy-owned and managed repository focuses and accelerates
research, providing a way for many advocacy groups to build a valuable
resource for scientists. “Our
organization has longed for the day when we can focus research with this
resource and create a dynamic consortium of researchers driving toward
the same goal — accurate and timely diagnosis followed by effective
treatment of inflammatory breast cancer,” said Owen Johnson, president
of the Inflammatory Breast Cancer Research Foundation, another
organization co-founding the BioBank. The
other founders of the bank are CFC International, Joubert Syndrome
Foundation, National Psoriasis Foundation, Noonan Syndrome Support Group
and PXE International. The
Genetic Alliance BioBank~ follows a model established in 1995 by PXE
International. That rare disease organization has initiated and
conducted research on pseudoxanthoma elasticum (PXE), actively
participating in the gene discovery and patenting.
PXE International and the other groups came together through
their work with the Genetic Alliance, a coalition of over 600 advocacy
organizations. These founding members developed standardized model
documents for the bank, designed and approved by the Genetic Alliance
BioBank Institutional Review Board. Researchers
who wish to receive samples submit an application to the
disease-specific advocacy organization. These organizations then release
coded samples to the researcher and hold the key that connects specific
samples to individuals, offering a unique opportunity for follow-up
studies while protecting participant confidentiality. The
Genetic Alliance BioBank~ will also provide an opportunity for
cross-disease research that may shed light on pathways and causes for
both common and rare diseases. The BioBank represents the next generation of patient advocacy, said Genetic Alliance BioBank~ founding President Sharon Terry. “But this is only the beginning. We are managing this resource, this community, with our eye on the prize — we will positively impact health outcomes. Solving these problems is often the work of generations, but we are taking one giant step in our lifetime.”
|
|
|
|
August 2004 A Chicago researcher who received a grant from the NBIA Disorders Association reports that he is making progress in using a mouse model to study a form of the disease known as pantothenate kinase-associated neurodegeneration, which affects about half of the people with NBIA. Dr. Han-Xiang Deng of the Northwestern University Feinberg School of Medicine is using gene-targeting techniques in his research. The goal of his project, for which he was awarded a grant, is to learn how chemical changes contribute to the disease so that useful therapies can be developed. Deng said his lab’s first two attempts at gene-targeting techniques did not succeed, but that the work yielded useful information. “We have made considerable progress in targeting the PANK2 gene responsible for PKAN,” he said. “Our current strategies are based on the lessons learned and we should soon have the knock-out mouse model for PKAN.” If the work proceeds as planned, the new mouse model will enable Deng and his crew to study how PKAN develops and “a rational approach to its treatment,” Deng said. |
|
|
|
April 2004 By
Patricia Wood Thanks to a grant from the Wright Family Foundation in September, our organization will be on the front lines of an effort that we expect to reap huge benefits for NBIA research. The $50,000 foundation grant will be used to cover the estimated five-year costs of joining the Genetic Alliance Bio Bank. This bank will store blood and tissue samples from patients with various disorders. These samples will be used for research purposes, so scientists can learn more about NBIA and other disorders. The ultimate hope, of course, is that researchers will discover cures for the diseases being studied. Patient advocacy groups representing these individuals, such as the NBIA Disorders Association, will own the samples. It is less expensive to have a group form a bio bank, rather than each organization trying to go it alone. But there also is power in numbers. Together, our organizations can mentor and support one another as we learn more about the illnesses affecting our members. The bio bank also can empower advocacy groups to work more closely as partners with the researchers. The hope is that the bio bank will make the research more streamlined and coordinated so that beneficial treatments can be gotten to patients more quickly. Often,
research into rare disease is hampered because the number of
samples being used in studies is very small, too small to give a
clear picture of the disease. This can lead to inaccuracies in how the
disease is described in the medical literature. Also, researchers don't
typically follow up on affected individuals after they donate, so
the progression of symptoms is not seen and valuable information is
lost. Many
times, affected individuals and their families never hear back about any
research findings on tissue donations. And some researchers are
reluctant to share their samples with colleagues or may have legal
problems doing so because of regulations. With a bio bank, researchers given access to samples will report back to the NBIA Disorders Association on their results, and the organization will inform families. If the bio bank lives up to its potential, it can change the way research is being done today. There are a variety of advantages for those who participate. Privacy and confidentiality are assured for those donating blood and tissue samples. Only samples stripped of identifying information are given to researchers. Affected individuals and their families only have to donate once, rather than multiple times for different research projects. Donors go through a consent process to help them make the decision freely before participating. Researchers have access to samples that follow the same collection and storage protocols and access to follow-up data. A goal is to have a research database that will help researchers and pharmaceutical companies study similar symptoms across different diseases, possibly opening the door to new treatments.
Dr.
Susan Hayflick, a key NBIA researcher, said she strongly supports the
decision to join the bio bank. "A significant hurdle to attracting new researchers to study a rare disorder is limited access to tissues," Hayflick said. "Most scientists are not physicians and so do not have a patient connection for obtaining tissue for their studies. Just as fundraising has encouraged and supported new NBIA investigators, better access to tissue will remove a key barrier to progress in understanding and treating the NBIA disorders. Participation in the bio bank is a very wise way for the NBIA Disorders Association to support research." The Genetic Alliance Bio Bank is still in its infancy. It was incorporated on Oct. 14 in Delaware with Sharon Terry as president, husband Patrick Terry as secretary and Joan Scott as treasurer. Sharon Terry also is president and chief executive officer of the Genetic Alliance, an organization that helps individuals and families living with genetic conditions. She is the founding CEO of PXE International, a non-profit dedicated to finding a cure for pseudoxanthoma elasticum. She’s on numerous advisory boards at the National Institutes of Health, Johns Hopkins University and the Centers for Disease Control and Prevention, among others. Patrick Terry is the president of the International Genetic Alliance and the co-founder of Genomic Health, Inc., a business dedicated to improving the quality of treatment decisions for patients with cancer. Joan Scott is the Deputy Director of the Genetics and Public Policy Center in Washington DC. The bank’s estimated budget for 2004 is $97,182. Seven organizations, including ours, have joined and agreed to pay entry fees of $13,883 each as founding members. Annual fees in future years will either be $5,000 or $10,00, depending on how many groups join. |
|
|
|
December
2003 Two more $30,000 grants awarded in September to advance research into NBIA The NBIA Disorders Association Research Fund has awarded two more grants worth $30,000 each to help scientists advance their understanding of neurodegeneration with Brain Iron Accumulation. Money for these grants comes from fundraisers and donations earmarked specifically for scientific research. This is the second consecutive year that the National Organization for Rare Disorders has administered competitive research grants on behalf of NBIA Disorders Association. Last year, NORD awarded three $30,000 grants on our behalf. One of the winners, Dr. Susan Hayflick, whose lab was involved in the discovery of a gene responsible for a form of NBIA, received a second $30,000 from NORD in September. Hayflick's latest project will study rationale therapies for pantothenate kinase-associated neurodegeneration (PKAN). PKAN is a genetic neurodegenerative disorder of children and adults with dystonia, retinopathy and high brain iron. It is caused by the PANK2 gene, the gene Hayflick helped discover. Potential therapies will be investigated by using fruitfly and mouse models of this disease. These studies will serve as a foundation for future research into treating humans with PKAN, a form of NBIA. The second grant NORD awarded in September went to Dr. Natalie Canham of Birmingham University's section of Medical and Molecular Genetics. She will look for the gene responsible for another form of NBIA. Her goal is to find mutations in the gene. That will lead to genetic testing for members of families affected by this condition. In the long term, such information will provide an understanding into the causes of NBIA. With last year's grant, Hayflick teamed up with researcher Dr. Penny Hogarth to bring NBIA patients and their families to the Oregon Health & Science University in Portland for a study. There, families were able to tour the research lab and meet those involved in NBIA research. Each participant in the study also underwent two procedures; a flash electroretinogram and magnetic resonance spectroscopy, which were discussed in detail in our August newsletter. The team is continuing to recruit families. If interested, contact Allison Gregory at (503) 494-4344 or gregorya@ohsu.edu. |
|
|
|
December
2003
Leaders of lay advocacy groups representing rare diseases, including the NBIA Disorders Association, had a chance to present their research needs and seek guidance from experts at the Office of Rare Diseases. The opportunity came during the Genetic Alliance conference in August when Stephen Groft, director of the Office of Rare Diseases, chaired a focus group to hear from us.
Groft's office, which is part of the National Institutes of Health, has a budget of $11 million in 2004 to support and stimulate research of rare diseases. The focus group discussed the upcoming establishment in 2004, of a network of seven clinical research centers across the United States which will focus on rare diseases, of which there are 6,000 disorders affecting more than 25 million Americans.
Obviously, there is a need for people to have champions, such as this federal agency, to help get researchers interested in their disease.
We discussed ways to create research partnerships with scientists, how to tap into the financial and educational resources of the National Institutes of Health and various ways to help cover travel costs for patients taking part in clinical studies -- a problem directly related to rare diseases with so few patients spread throughout the world.
Another important topic was how the national institutes could help finance scientific workshops on rare diseases. As a result of my participation in this focus group, the seed was planted for a second scientific workshop in NBIA disorders, tentatively scheduled for Spring, 2005. We will once again have researchers from around the world gather together to collaborate, exchange information and brainstorm about the disease. This is a wonderful opportunity to further research, as well as stimulate new researchers to study NBIA.
In addition to this focus group, I was also invited to attend a regional training workshop sponsored by the Office of Rare Diseases and the U.S. Dept. of Health and Human Services on "Gaining Access to Research Resources." There was no charge to attend and a stipend was given to cover travel costs. It was held Nov. 7 to 9 in San Francisco and provided valuable information on understanding how research is done at the National Institutes of Health.
I am grateful the institutes are attentive to our needs. Through opportunities such as the focus group and training workshop, the agency has shown it is willing to listen, partner, and financially support research into NBIA through scientific workshops and grants to individual researchers. |
|
|
|
October,
2003 Two Research Grants awarded by NORD/NBIA Disorders Association |
|
The
recipients are: Natalie Canham, MB Funding: $30,000 for 1 year Dr. Canham of Birmingham
University’s section of Medial and Molecular Genetics will look for
the gene responsible for a variant form of Neurodegeneration with Brain
Iron Accumulation. Dr. Canham’s goal is to find mutations in the gene
to be able to offer genetic testing to members of families affected by
this condition. In the long term such information will provide an
understanding into the causes of NBIA. Funding: $30,000 for 1 year |
|
|
|
August 2003 OHSU investigators to examine PKAN in
families this summer Our quest to learn more about
Pantothenate Kinase-Associated Neurodegeneration, or PKAN, got a boost
in June when we enrolled the first participant in a clinical study at
the Oregon Health & Science University. PKAN is a disorder
that is related to NBIA, and we will be studying more families with PKAN
throughout the summer. Each person who takes part in the
study will undergo two procedures: a flash electroretinogram, which we
hope will teach us more about the retinal problems observed in some
individuals with PKAN, and magnetic resonance spectroscopy, which we
expect to enhance our understanding of the chemical changes that occur
in the brains of affected people. Here are more details about both
tests: Electroretinogram (ERG) When the light enters the eye, it
triggers an electrical response from the photoreceptor cells of the
retina and the other cells that process the signal. The signal is sent
along the optic nerve to the portion of the brain that puts the picture
together for the person, all within thousandths of a second. The cells of the retina include two
types of photoreceptors called rods and cones. Cones provide central
reading vision and color vision and are more densely packed in the
middle area of the retina. Rods provide night vision and detect motion.
They are also more responsible for peripheral vision. By varying the
flashes of light used to stimulate the retinal cells, it is possible
through this ERG test to selectively stimulate some cells more than
others, such as rods more than cones. In this way, the function of a
certain type of cell can be analyzed. Because some individuals with PKAN
have progressive loss of peripheral vision and retinopathy, or disease
of the retina, it is helpful to assess different cells of the retina
with ERG. In classical PKAN, ERG has shown characteristic changes that
reflect rod photoreceptor degeneration specifically. These types of
changes may be found by ERG before any vision loss is detected in
affected individuals. It’s important to establish typical ERG results,
or “norms,” so that when doctors have new therapies to try, they
will be able to determine the effects of these interventions. The test is done by wearing contact
lenses with small wires that conduct the signals to a computer. The
responses are recorded and compared with those from control subjects.
Before starting, the pupils are dilated and topical anesthetic drops are
given to make wearing the contacts more comfortable. The test does not
hurt, but it does require that individuals hold still and look straight
ahead. This has been one of our challenges for the study, since dystonia
can make it so difficult for individuals to hold still for long periods
of time. Magnetic Resonance Spectroscopy (MRS) Certain chemicals have been
identified as markers for various brain changes. N-acetylaspartate (NAA)
levels decrease when the axons of nerves have been damaged. Choline
levels rise when there has been breakdown of the brain’s support
structures. Choline is released from cell membranes, fats, and myelin,
the lining around the nerves that serves as insulation. Changes in
creatine and lactate can reflect alterations in brain energy metabolism,
and lactate also increases when brain cells have been deprived of blood
flow. Charting what is happening with these various chemicals in NBIA
individuals will help us in the future to know whether interventions
have affected them in significant ways. The applications of this technology
are growing rapidly. For example, recent research conducted at Loma
Linda Medical Center in California suggests that MRS may be a very
accurate tool for predicting outcome after traumatic brain injury. In
the Loma Linda study, an MRS performed only seven days after a brain
injury could help predict how a patient would be functioning six months
later. Measurement of NAA levels in persons diagnosed with multiple
sclerosis has also been found to help predict prognosis, and some
patients with Alzheimer’s disease and Parkinson’s disease are now
having their treatments determined, in part, based on MRS results.
Since MRS has not been used in the
small population of persons diagnosed with PKAN, we hope it will shed
some light on the biochemical changes occurring in the brains of
affected individuals. Although we know there is atypical iron
accumulation in the brain, it is not clear why this happens or how it is
related to the neurodegeneration observed in people with PKAN. Looking
at additional markers to assess damage of brain structures and brain
energy metabolism may help us to better understand the disease and, we
hope, give us some leads regarding potential treatments |
|
|
|
April 2003
Research
NBIA Disorders Association is
sponsoring two, $30,000 seed grants through the National Organization
for Rare Diseases in 2003. If you would like further information,
please go to this link NORD-RFP.
As you know, three grants were made available in 2002. Those
research projects are now underway.
Thanks to all who sent in donations in December to help fund the two new grants. We fell short of our goal of $10,000, but the board voted unanimously to take money from the General Fund so we would not miss this opportunity. We still have adequate resources to handle our expenses. Notices have gone out to hospitals, universities, researchers and medical journals asking for abstracts by March 15, 2003. It was also a wonderful opportunity to make everyone aware of the new name of the disease and our organization at no additional mailing costs. These research grants are vital to encouraging new researchers to study our disease. In February, NBIA Disorders Association was contacted by a researcher who received the RFP (Request for Proposals) notice sent out. He decided our disease was one he would like to study and plans to apply for one of the grants. This is how our organization can make a difference and help research move forward more rapidly. Please continue to support our Research Fund through your donations and fundraising efforts. Research Update on 2002 Grants Awarded New PKAN study underway at OHSU A new study of individuals with pantothenate kinase-associated neurodegeneration, or PKAN, is about to get underway at the Oregon Health & Science University. It will be led by Drs. Susan Hayflick and Penny Hogarth, who each were awarded grants of $30,000 last year from the NBIA Disorders Association. The association made three such awards last year, its first ever, and will make two more $30,000 awards later this year. Hogarth and Hayflick are combining their awards to collaborate on this new study, which will investigate the specific features of PKAN and how the condition progresses over time. About 25 patients of all ages, in both early and late stages of PKAN, will travel to OHSU in Portland, Ore., for a three-day visit to give the researchers a chance to do a variety of assessments on them. The patients and their travel companion will be accommodated at a research support center at the hospital. Although anyone with PKAN knows from experience that the disease features progressive movement disorders and involves several body systems, the researchers want to study PKAN systematically. By assessing 25 patients in different stages, a large amount of data will be gathered to better characterize the signs and symptoms of PKAN and how it progresses over time. The knowledge gained from this work will lay the foundation for future research, particularly when clinical trials begin for testing possible treatments. Now that the causative gene, PANK2, has been found, and the biochemical basis of PKAN is better understood, it is hoped that the OHSU studies may also point the researchers toward potential treatments. The researchers will use a sophisticated type of MRI with spectroscopy, which assesses the brain for various levels of chemicals. An electroretinogram, or ERG, will also be performed to look for changes in the photoreceptors in the back of the eye. Although many individuals with PKAN eventually develop retinal abnormalities, it is suspected than an even higher number may have changes detectable by ERG. Also during the three-day visit, a diet assessment, physical and neurological examinations, and blood and urine studies will be done. Hayflick and Hogarth plan to use several standardized testing tools, such as a dystonia scale, quality of life scale and intelligence testing to look at the many aspects of living with PKAN and how it affects an individual’s life and function over time. Patients will begin coming to OHSU for the testing within the next few months. OHSU genetic counselors Jason Coryell and Allison Gregory are contacting eligible families about the study. Interested families may also contact them for more information at (503) 494-4344 or to coryellj@ohsu.edu or gregorya@ohsu.edu. Mouse model in progress Dr. Han-Xiang Deng of Northwestern University Medical School in Chicago, Ill., was the recipient of our third research grant in 2002. He says his lab has begun the work of generating a NBIA mouse model—a process that generally takes approximately one year to complete. Dr. Deng will keep us informed as to the progress of this project. |
|
|
|
December 2002 HSSA awards first-ever research grants to three scientists |
|
HSSA has awarded its first research grants — a total of $90,000 — to three scientists seeking to better understand HSS and how to treat it. A scientist who has worked closely with HSSA since its inception, Dr. Susan Hayflick, a physician and geneticist at the Oregon Health & Science University, is among the recipients. The National Organization for Rare Disorders handled the advertising, screening and selection of these competitive awards on behalf of HSSA for a cost of $5,000 per award. Along with Hayflick, Dr. Penelope Hogarth, a neurologist who also works at the OHSU, and Dr. Han-Xiang Deng of the Northwestern University Feinberg School of Medicine received the grants. Hayflick and Hogarth plan to put their grants together, a combined $60,000 and work jointly on a study to measure how the disease progresses. They plan to investigate biochemical changes in people with the impaired gene, PANK2, that causes pantothenate kinase associated neurodegeneration (PKAN). The PANK2 gene was discovered last year by Dr. Jane Gitschier’s lab at UCSF, in collaboration with Hayflick’s team at OHSU. Hayflick and Hogarth will examine patients in early and late stages of PKAN. By comparing mild and severe cases, they hope to identify aspects of the disease that change as it progresses. While it’s obvious to most families that there are progressive changes, tools to measure those changes over time have never been developed. Once measurements are identified, clinical trials can proceed to give doctors and patients more objective information about the effectiveness of a treatment or drug. Clinical trial data is crucial when making treatment decisions because the results reflect a group’s experience rather than the subjective report of what worked for one patient. Hayflick and Hogarth plan to bring patients to OHSU in Portland for a brain MRI with spectroscopy. The MRI will use a higher strength magnet than most standard MRIs so the doctors can compare patient data from the same equipment. Spectroscopy studies use the same MRI machine to help determine levels of certain chemicals in the brain. These results have not been studied systematically in the past. In addition, patients in the study also will have an electroretinogram (ERG), which is a non-painful procedure to record electrical activity in the eye. The doctors will conduct physical examinations, collect blood and urine samples and gather information on medical and nutritional history. Deng will develop a mouse model of PKAN using gene targeting techniques. Deng intends to investigate how the disease works and what potential drugs might be useful for therapeutic testing. PKAN, which is now being defined as a disorder under the NBIA umbrella, is a neurodegenerative disease that is caused by a block in an enzyme that converts vitamin B5 (pantothenate) to coenzyme A, an important compound for energy and fat metabolism. The goal of Deng’s project is to learn how chemical changes contribute to disease so that useful therapies can be developed. For the Hayflick/Hogarth study, OHSU genetic counselor Jason Coryell will be sending information to families with known PANK2 mutations this fall. Any questions regarding participation in the study may be made directly to him at coryellj@ohsu.edu or (503) 494-4344. |
|
|
|
September 2002 NORD/HSSA Research Awards for Hallervorden-Spatz Syndrome |
|
The
three researchers who will receive these grants and the work they will
be studying are as follows: Dr.
Han-Xiang Deng of the Northwestern University Feinberg School of
Medicine will develop a mouse model of Hallervorden-Spatz
syndrome (HSS) by targeting mouse pantothenate kinase (PANK2)
gene. HSS is a rare neurodegenerative disease with massive iron
deposition in the brain. The pathogenesis is not known and there is no
effective treatment. Dr. Deng’s goal is to establish a mouse model to
investigate the pathogenesis of HSS and to explore potential drugs for
therapeutic testing. Dr.
Susan Hayflick, a medical geneticist at Oregon Health & Science
University, will
investigate biochemical changes in people with pantothenate
kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz
syndrome). PKAN is a neurodegenerative disease that is caused by a block
in an enzyme that converts vitamin B5 (pantothenate) to coenzyme A, an
important compound for energy and fat metabolism. The goal of the
project is to learn how chemical changes contribute to disease so that
rational therapies may be developed. Dr. Penelope Hogarth, a neurologist at Oregon Health & Science University, will evaluate clinical measures of disease in people with pantothenate kinase-associated neurodegeneration (PKAN) previously known as Hallevorden-Spatz syndrome. This disorder of vitamin B5 metabolism affects children and adults and causes an abnormal accumulation of iron in the brain, leading to gait problems, involuntary movements, speech and swallowing difficulties, and vision changes. Dr. Hogarth’s goal is to provide tools for the assessment of future treatments for the disease. |
|
|
|
Fall 2002 |
|
Now that our Research Fund has $104,177 in its coffers, thanks to the huge successes of a Bowl-a-thon in March and a 5K Walk/Run in August, HSSA is ready to get the ball rolling on its first research grants. The Board of Trustees voted Nov. 10 to send $105,000 to the National Organization for Rare Disorders to administer HSSA’s research grant program. The general fund will lend the remaining $823 difference so that three one-year grants valued at $30,000 each can be made. NORD requires that $5,000 be paid to administer each grant to cover the costs of advertising, screening and monitoring proposals. HSSA, on its own, does not have the resources to do this intensive work but may develop that expertise in the future. In the meantime, the board was unanimous in wanting to move forward with awarding research grants as quickly as possible. NORD offered the best solution—and at a bargain price considering the costs and work involved. The grants act as “seed money” to stimulate new research into treatments or diagnostic tests. They enable scientists to gather data to attract larger multi-year government grants, or if applicable, a commercial sponsor willing to manufacture an orphan drug or therapy. In January, NORD will publish a request for proposals in major medical journals, in addition to sending notices to all medical schools in the United States, academic research facilities, international research institutions and others in NORD’s clinical database. The initial RFP asks scientists to submit a brief description of their proposed project along with their qualifications and a draft budget. The medical advisory committee evaluates the proposals using “peer review” procedures established by the National Institutes of Health. The committee then selects finalists and invites them to submit a detailed research proposal. Those will be due in June or July. Scoring of the grants is done individually by each medical expert using the NIH scoring system and scores are added together to determine a final ranking of each proposal. Any reviewer with a conflict of interest is excused from voting on a specific proposal. Grants must be approved by NORD’s board, and winners will be announced in September or October. HSSA will be listed in the researcher’s publications resulting from these grants as the donor of funds. If you have any questions or comments on this process, please contact president, Patricia Wood, at pwood@NBIAdisorders.org. Research news for 2000 and 2001 can be found on this web site by clicking on this link. |