As the NBIA community grows with more disorders under its umbrella, the organization’s research agenda also is evolving as some families seek more attention—and dollars—for their loved one’s disorder.
That was among the topics discussed by families, the NBIA Disorders Association board and its Scientific & Medical Advisory Board at a meeting on research priorities. It was held during the association’s 20th anniversary celebration in the Cincinnati area.
Although no final decisions were made, the open discussion provided a valuable learning experience as each group shared ideas.
Among the priorities listed by researchers were these:
- Improving existing mouse models and creating new ones to study
- Placing an emphasis on “natural history studies” in NBIA individuals to document changes as the disease progresses
- Understanding how Coenzyme A, a molecule essential to carbohydrate and fat metabolism, affects NBIA diseases
- Establishing biomarkers—compounds typically found in blood, urine or fluids that indicate disease, its severity and how the body is responding to treatment
The board said it plans to work with its Scientific & Medical Advisory Board, along with other leading NBIA scientists, to set research priorities for each NBIA disorder. This is an important step to putting out a research grant application call dedicated to a specific disorder. Past requests for these research proposals have been open calls to study any NBIA disorder.
As a result of a change the board made last year to allow research donations over $1,000 to be earmarked for a specific disorder, fundraising is close to supporting a $45,000 grant for two disorders.
The downside to this change is that we no longer receive enough donations to support an “open call” for grant applications. This affects our ability to fund research that finds new genes, finance our International Patient Registry for all NBIA disorders (including the collection of natural history studies) and fund other promising research that may foster new ideas, said Patricia Wood, the association’s president.
Dr. Susan Hayflick, a key NBIA researcher from the Oregon Health and Science University, said that research on one NBIA disorder often leads to insights on another. For example, she said, the discovery of PKAN and INAD genes “opened our eyes” to new avenues of study. Those discoveries focused researchers’ attention on mitochondrial membrane defects as a common theme in NBIA disorders and informed ideas about the disease process in FAHN and MPAN, she said.
Further, her team’s work on a grant to devise best practices for PKAN “has a lot of relevance to other NBIA disorders,” she said.
It wouldn’t make sense for the board to put all of its research money into disease-specific research grants, she added.
Michelle Roland of Logansport, Ind., who has a child with BPAN, said she at the meeting that she “didn’t know until today that wanting to fund what was wrong with my kid” might not be the best approach.
One suggestion made at the meeting was that 10 percent of the money raised for a specific disorder go into an “open call” fund, so that type of research can continue.
Dr. Penny Hogarth, who is part of the OHSU team, reminded the board that an open call for proposals led to the discovery of the BPAN gene. She was then able to tell the brother of a BPAN-affected individual he had near zero chance of having the gene mutation, Hogarth said. He went on to have two children without BPAN.
Hogarth emphasized that a missing link in the quest to better understand NBIA are natural history studies, which are needed to inform drug development and other therapies for treating those patients.
“Unless I understand the natural trajectory of the disease, how it progresses over time, I don’t know if my treatment is doing anything,” she explained.
Just because a child with a particular NBIA disorder has seizures does not necessarily mean that seizures are part of the disease, Hogarth said.
The board asked if families wanted to have grant funds spent on studies of clinical symptoms such as seizures in NBIA disorders, since they impact daily life so profoundly. One BPAN parent said there are already many studies on seizures and advised against spending scarce dollars that way, while a few others said a better understanding of seizures might be helpful.
Michael Wichert, an MPAN parent from Hudson, Ohio, said he sees little awareness of NBIA and urged more advocacy work, including with members of Congress. Hayflick said parents are uniquely qualified to draw attention to NBIA and the need to fund rare diseases.
Collaboration with other NBIA researchers is critical, Hogarth said, adding that researchers working on other, more common disorders, such as Parkinson’s disease, are not as interested in teaming up with a rare disease organization.
Asked about using medical marijuana for NBIA disorders, Hogarth said that marijuana is challenging because dose and composition vary but that research is underway on this.
The board agreed our family conference next June is an excellent opportunity to continue the research discussion with families. It plans to hold a session to discuss how research grants are awarded, how research on one disorder helps facilitate advances in another and related issues. That way, many more families can ask questions and share ideas, while gaining a deeper understanding of why the board makes certain decisions.