NBIA NEWS & INFORMATION

2024 Million Dollar Bike Ride Results in $75,141 BPAN Research Grant

by Patricia Wood

Dr. Young-Ah Seo from the University of Michigan School of Public Health in Ann Arbor, Michigan, is the recipient of a $75,141 BPAN research grant as a result of fundraising by NBIA families and friends for the 11th annual Million Dollar Bike Ride.

Dr. Young-Ah Seo from the University of Michigan School of Public Health in Ann Arbor, Michigan, receives 2024 MDBR BPAN grant award.

The annual ride is hosted by the University of Pennsylvania’s Orphan Disease Center which provides a $30,000 match for the funds raised. Our organization has participated since 2018, resulting in 11 BPAN research grants funded with the help of this yearly event.

The title of Seo’s project is “Charting WDR45-dependent genes for neurodegeneration at a single-cell resolution.” Her focus is on uncovering the underlying causes of neurodegeneration in BPAN.

To conduct this research, Seo will study a mouse model where the Wdr45 gene has been deleted, using single-cell RNA sequencing to analyze changes in gene expression at the individual cell level. This is accomplished by taking brain tissue from the mouse model and breaking it down into individual cells. By sequencing the genetic instructions (RNA) from each cell, researchers can see which genes are active or disrupted, helping to understand how WDR45 loss affects different brain cells. This work will help identify the specific brain cells and molecular pathways that are most affected by the absence of Wdr45.

“Mapping these pathways helps us pinpoint new targets for potential therapies by identifying the key processes that go wrong when Wdr45 is missing. If we find that certain pathways — such as those controlling cell survival, energy production, or waste removal — are disrupted, we can look for existing drugs or develop new treatments that restore these functions, potentially slowing or preventing neurodegeneration in BPAN,” Seo says. “This project could pave the way for developing treatments that address the root causes of BPAN, benefiting patients with this rare condition.”

Seo’s previous research has focused on brain-iron overload and iron-induced neurodegeneration in BPAN patients. She was also the recipient of the 2021 Million Dollar Bike Ride grant with her proposal titled, “Reversing Brain Iron Overload in BPAN by a Natural Small Molecule.”

When asked about the role of brain iron in BPAN, she said, “I think that brain iron plays a role in BPAN, but it may not be the root cause — it could be a consequence of disrupted cellular processes due to Wdr45 loss. Our study will help clarify whether iron buildup is driving neurodegeneration or if other factors come first.”

If successful, this research could lead to therapies that restore normal cell function. Potential treatments might include drugs that help clear waste more efficiently, protect neurons from stress, or even regulate iron balance in a controlled way.

Global Collaboration Highlights Progress at First BPAN Research Roundtable

By Amber Denton

In early October, the NBIA Disorders Association hosted the first BPAN Research Roundtable, bringing together thirteen nonprofit organizations from around the world that are leading efforts to fund and advance research into Beta-propeller Protein-Associated Neurodegeneration (BPAN). Since its discovery in 2012, BPAN has grown to become the most common NBIA disorder.

As the BPAN landscape has evolved, many families affected by the disorder have founded additional nonprofit organizations dedicated to funding research. They are joined by our fellow international NBIA Alliance organizations which, similarly to our organization, also support research into all NBIA disorders.

The roundtable included representatives from thirteen global organizations:  NBIA Disorders Association (USA), Don't Forget Morgan Foundation (USA), Isabel's Chance (USA), Duets Across America (USA), Action for BPAN (UK), Hope for Hermione (UK), BPAN France (France), BPAN Spain (Spain), Hoffnungsbaum e.V. (Germany), AISNAF (Italy), NBIA Poland (Poland), Stichting Ijzersterk (Netherlands), and NBIA Suisse (Switzerland).

The purpose of the roundtable was to ensure all organizations were up-to-date on ongoing research efforts in order to avoid duplicating work and to identify areas requiring further focus. Most importantly, the meeting reinforced a shared commitment to a common goal: finding effective treatments and ultimately a cure for BPAN. Since 2012, the research community has made significant advancements in understanding the disease and the participating organizations were proud to share progress in several key research areas.

One focus was sharing the status of current patient registries and natural history studies, which are essential for understanding the full spectrum of BPAN’s impact. These efforts track disease progression over time and provide valuable insights into potential treatment options.

Other areas of research discussed included autophagy, mitochondrial dysfunction, ferroptosis and biomarker identification. Understanding the cellular mechanisms behind BPAN is critical for developing therapies that can address its symptoms and measure their effectiveness. The group also discussed the need for development of a small molecule and advancing gene therapy initiatives. Both of these approaches could directly address the genetic causes of BPAN, offering hope for targeted a treatment.

Additionally, discussions also focused on FDA-approved compounds that are actively being screened and further studied in animal models. The hope is to identify drugs that have already been approved for other medicinal purposes that could be used off-label to improve symptoms of BPAN.

The roundtable also highlighted progress in creating consensus guidelines for the medical community and establishing NBIA Centers of Excellence and BPAN-specific clinics. These efforts are vital for ensuring families receive high-quality, specialized care while advancing research into the disorder.

With research institutions worldwide investigating various aspects of BPAN, the importance of continued collaboration has never been clearer. As Christian Magnet of BPAN France emphasized, “Act together to do better faster.” By sharing information and ideas, organizations can align their efforts, maximize resources and ensure their work complements one another.

Looking ahead, the organizations involved in the roundtable are committed to maintaining momentum and staying closely connected. Regular meetings every six months will help ensure that research efforts remain focused on the areas with the greatest promise.

“It was such an inspiring session to be a part of as a newly registered charity. It’s really valuable to start relationships with others in the world on a very similar path, filled with even more hope that we can beat BPAN and provide our kids with a much better-than-predicted future,” said Kelly Sayers of Action for BPAN. This sentiment reflects the shared optimism of the organizations that collaboration will accelerate progress toward meaningful breakthroughs for BPAN families.

Christina Ftikas of Don’t Forget Morgan Foundation added, “Collaboration and research efforts across BPAN foundations will only help the community get to the finish line faster and hopefully lead to further development of a treatment for our beautiful children.” The importance of these joint efforts cannot be overstated as the BPAN community continues to move forward with hope and determination.

This ongoing collaboration highlights the strength and commitment of the BPAN community. Together, these efforts are bringing us closer to a time when effective treatments and a cure are within reach.

By: Amber Denton

It is with a heavy heart that we inform the community that CoA Therapeutics has decided to discontinue the clinical trial of BBP-671, the compound the company was developing as a potential treatment for Pantothenate Kinase-Associated Neurodegeneration (PKAN). This decision was made after studies showed they were unable to identify a clinical trial dose that adequately balanced safety (toxicity) and potential clinical benefit.

In March, we shared that CoA Therapeutics announced a delay in their PKAN clinical trial due to the need for additional laboratory studies on BBP-671 to determine critical dosing and safety information. A significant challenge identified during these additional studies was the wide variability of BBP-671 blood levels observed in humans. Individuals taking the same dose of BBP-671 showed vastly different blood concentrations of the drug. This inconsistency posed a significant risk in determining an appropriate and safe dose for PKAN patients.

Toxicology studies in animal models of PKAN helped to establish a specific safety limit, or target blood level, for BBP-671 that cannot be exceeded due to safety and FDA regulations. The target blood level needed for efficacy was shown to be dangerously close to the safety limit.

Despite multiple studies and efforts to control these large differences in human blood levels, the exact cause of these variations remains undetermined, making it impossible to predict individual responses to the drug. Some individuals may have exceeded the safety limit, while others might have fallen below the target level, resulting in no clinical benefit.

Originally discovered through research led by St. Jude Children's Research Hospital in Memphis, Tennessee, CoA Therapeutics will return ownership of BBP-671 and related compounds to St. Jude. All their research data will also be shared to support any future research.

We are immensely grateful for the long-standing partnership with CoA Therapeutics. Their dedication to the NBIA community will not be forgotten. We appreciate their passion and desire to find a treatment for our PKAN families, and the amount of empathy and determination demonstrated year after year on behalf of our families.

CoA Therapeutics has released a detailed official announcement that you can read here along with their heartfelt message to the community