An NBIA Disorders Association intern describes growing up with an affected sibling

April 2022

By Katherine Fox


Kevin and me at one of his
Miracle League Games, circa 2010.

The bond between siblings is undeniably special, but being the sibling of someone who has a disability has its own kind of uniqueness. My older brother, Kevin, was diagnosed with PKAN when I was very young. And even as the youngest of three children, I was a close participant in Kevin’s NBIA journey.By age 7, I was much more acquainted with doctor visits and hospitals than my peers. But I also was introduced to an amazing community of people who I otherwise wouldn’t have known.When I was about 10, most of my Friday nights were spent at Kevin’s Miracle League games, a guaranteed bright spot in my week.

It was comforting gathering with others who understood the intricacies of how a family dynamic is shaped when someone has special needs. The sense of community at those events was indescribably special, and I felt extremely lucky to be a part of it. I’ve learned there’s a lot you can’t control when you grow up with a terminally-ill sibling. I couldn’t control how he felt, the status of his health or the available treatment options. It was hard at times, but witnessing Kevin’s never-ending strength and perseverance helped me through it all.At the end of the day, there was nothing better than seeing his huge smile while we watched “Sesame Street” every night. Little moments like that are among my most cherished. When I entered the scary world of high school, Kevin’s smile had the power to make any school stress or drama fade into the background.


Kevin, our sister Madeline, and
me on his 20th birthday.

Although I didn’t have much involvement with the NBIA Disorders Association as a child, I knew as I grew older I wanted that to change. As part of my undergraduate degree, I am required to complete an internship with an organization of my choosing. I’ve been fortunate to do that internship with NBIA Disorders Association. It has helped me grow as a writer and learn so much about NBIA, and, in turn, my brother. Now I feel closer to him than ever, and I’m grateful that this educational experience gave me that opportunity.



Dr. Susan Hayflick named Rare Champion of Hope

Hayflick awardDecember 2021

For her deep commitment and enduring service to the NBIA community,  Dr. Susan Hayflick of the Oregon Health & Science University received the “Rare Champion of Hope in Medical Care and Treatment” award from Global Genes. 

This award celebrates medical and health care professionals who have made significant contributions to clinical care and treatment of rare conditions. Hayflick was nominated by the NBIA Disorders Association Board of Trustees in recognition of her 30 years of dedication to the NBIA community. 

Global Genes, a leading rare disease patient advocacy organization, annually recognizes and celebrates inspiring individuals who work to improve the lives of individuals with rare disorders. It presented the 2021 awards at a ceremony in Philadelphia in November, held in-person and virtually.

“Dr. Hayflick is the one constant who has been working on NBIA since before most of

us ever heard of it,” NBIA Disorders Association Vice President Mary Ann Roser said on behalf of the board. “She is a source of hope for all of us — for NBIA individuals, their families, the board members and the entire NBIA community.”

Hayflick thanked the worldwide NBIA community for the award, saying, “you are my family.” She spoke of being driven by hope, calling it her “fuel” and “the glue that holds groups together, whether in a laboratory, or at home or in an advocacy community. …Without hope, there is not a path forward, but with hope, everything is possible.”

For the past 25 years, Hayflick has served as the director of the association’s Scientific & Medical

Advisory Board, in addition to being the premier NBIA researcher, expert and supportive physician-friend to patients and families the world over. Her journey began in Buffalo, New York, in 1991 when she received a call from a neurologist who asked for her opinion on a devastating neurological condition affecting three of the four children of an Amish couple who lived nearby. All three children were ultimately diagnosed with PKAN, one of the most common forms of NBIA. The family’s plight touched Hayflick heart and inspired her to look for the gene responsible for the disease.

She has since worked tirelessly to understand NBIA disorders and develop treatments for affected individuals. She, her team and collaborators around the world have discovered such NBIA genes as PANK2 for PKAN, PLA2G6 for PLAN, FA2H for FAHN and WDR45 for BPAN

At OHSU in Portland, Hayflick is a professor and chair of the Department of Molecular & Medical Genetics. Her lab is working with collaborators on a clinical trial for treating PKAN in which patients can receive the compound being tested, CoA-Z, in their community, without having to travel to Oregon. That innovation may become a model for the rare disease community on how to run a clinical trial in a way that prioritizes convenience for patients and families. Travel to a trial site is a known barrier to clinical trial participation, especially in the rare disease community.

In accepting the Rare Champion of Hope award, Hayflick told the audience to “find hope, foster hope, create hope, be hopeful, as I am.”



New $115,000 grant awarded to study possible PKAN therapy

December 2021

A Yale University professor has received a research grant worth $115,000 that could help lead to a treatment for PKAN, the second most common form of NBIA.


Choukri Ben Mamoun, Ph.D.,
at Yale University, receives grant
for $115,000 to study PKAN.

Choukri Ben Mamoun, Ph.D., a professor of medicine (infectious diseases) and microbial pathogenesis at Yale, won the “Best Presentation” award in Yale Lifesciences PITCHFEST 2020 for his work on a possible treatment for Pantothenate Kinase-Associated Neurodegeneration (PKAN). That award prompted three NBIA patient organizations—the NBIA Disorders Association, Hoffnungsbaum e.V., in Germany and AISNAF in Italy—to collaborate on making the grant, in August. 

Ben Mamoun also received the Blavatnik Award this year, which is awarded by the Blavatnik Fund for Innovation at Yale University to select projects after a competitive application process. The $300,000 award provides additional seed funding for the PKAN project.

The NBIA groups’ research grant to Ben Mamoun is titled “A High-Throughput Screen for PKAN Reversing Agents.” The goal is to look for small molecules that restore normal function in cells that are deficient in the PANK2 gene, which is impaired in PKAN individuals.

PANK2 directs the production of pantothenate kinase, which is involved in the execution of several essential biochemical reactions in the body. So, a drug that restores or mimics the function of the PANK2 gene could be effective in treating PKAN.

Ben Mamoun will look for small molecules to create a drug that can activate a second Pank enzyme to compensate for the loss of PANK2. The hope is such a drug could restore neurological function in PKAN individuals. The research also will evaluate the safety and efficacy of this novel treatment by conducting tests in the lab and in mouse models.

Previously, Ben Mamoun’s research focused on developing new antimicrobial compounds that do not inhibit human enzymes. Instead, Mamoun’s team discovered that their compounds not only inhibited the human enzyme but that nine of them activated it. That discovery fueled Ben Mamoun’s interest and opened up the possibility to treat PKAN by using the novel compound to activate the gene that causes PKAN.



Research expands BPAN knowledge on how iron accumulates in brain

December 2021


Dr. Young Ah Seo from the University of Michigan
School of Public Health in Ann Arbor, Michigan.
Work from this grant has been published in the
Journal of Neurochemistry.

Dr. Young Ah Seo’s recently completed research, “Defining the Roles of Iron in BPAN,”  has generated new information about how iron accumulates in the brains of individuals with Beta-propeller Protein-associated Neurodegeneration (BPAN), the most common form of NBIA. 

Seo, an assistant professor in the department of nutritional sciences at the University of Michigan School of Public Health in Ann Arbor, and her team, observed that the dysfunctional WDR45 gene in BPAN led to impaired iron storage in the brain, causing iron to build up to a toxic level that damages cells.

In 2018, Seo received the first-ever early-career research grant from the NBIA Disorders Association, for $150,000. Although the grant work was meant to be completed in two years, Seo received a one year, no-cost extension because of delays caused by the pandemic.

Her team’s goal was to identify the major proteins and pathways involved in iron accumulation when the WDR45 gene is deficient and how the altered iron uptake and metabolism contribute to neurodegeneration.

The WDR45 gene is involved in autophagy, a natural process that helps clear unnecessary materials from cells. Exactly how the mutated gene also leads to iron accumulation in the brain has not yet been fully understood, so Seo and her team sought to unravel the mystery.

They successfully generated a cell model of BPAN in which the WDR45 gene was deleted. They saw significantly elevated iron levels in this model, suggesting that it accurately mimicked the condition seen in individuals with BPAN.

They found that the absence of the gene’s protein, also named WDR45 (when not italicized it refers to the protein), led to significant changes in the pathways that are responsible for the uptake and regulation of iron in cells. This may be the basis of brain iron accumulation.

They also observed that the overload of iron in cells in this model was associated with impaired ferritinophagy. This is a form of autophagy that degrades a protein responsible for iron storage in cells, called ferritin. Essentially, the process that helps prevent excessive iron storage was impaired.

Finally, they observed that WDR45 deficiency led to excessive iron accumulation in the mitochondria, altered mitochondria metabolism and overproduction of toxic reactive oxygen species (unstable molecules that easily react and cause cell damage). This may contribute to the neurodegeneration seen with BPAN.

All together, these findings suggest a potential underlying cause of disease to explain how iron accumulates in BPAN. 

Seo’s work from this grant has been published in the Journal of Neurochemistry, titled “A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation”. She intends to seek new funding to expand on the project’s findings. 



Planned grant for MPAN research reflects joint effort with newly defined priorities

December 2021

The NBIA Disorders Association is teaming up with three European sister organizations to seek proposals for an MPAN research grant worth about $160,000.

Aisnaf logoThe collaborative grant-making effort has financial support from our organization, as well as AISNAF (Italy), Hoffnungsbaum e. V., (Germany) and Stichting Ijzersterk, (Netherlands). We are inviting selected researchers to submit a proposal for the Mitochondrial-membrane Protein-Associated Neurodegeneration (MPAN) study, with the aim of awarding a grant in May 2022.

Hoffnungsbaum logo.jpgThe call for proposals is the outcome of a coordinated process to identify MPAN research priorities. AISNAF, Hoffnungsbaum e.V., and our organization recognized the need for an MPAN Landscape Analysis in 2020, which is a comprehensive study of the global research done to date on MPAN. We reached this conclusion after failing to receive viable proposals in 2018 and 2019 for MPAN. We then hired Science Compass, led by Dr. Francesca Sofia, to facilitate the research review process.

Stichting logoThis included a thorough examination of the scientific literature on MPAN, NBIA, and other relevant diseases, as well as information from publicly available institutional websites and databases. Several researchers with longstanding expertise in NBIA disorders participated in interviews conducted between June and July 2020. The landscape resulting document provided a platform for discussions held during a two-day virtual workshop in October 2020. 

The workshop participants, including researchers, clinicians and patient organization representatives, identified and prioritized two key objectives for understanding and potentially treating MPAN.  

The first priority is to foster basic research that is crucial to advance our understanding of the C19orf12 gene that causes MPAN, and its associated protein. Although C19orf12 was discovered in 2011, its function and role in disease remains largely unknown. The disease accounts for approximately 5% of all NBIA cases. Between 2011 and 2019, a total of seven research projects studied MPAN, including those by our organization, NBIA Switzerland, NBIA Poland and Hoffnungsbaum e.V. But there is still much to be learned about this disease.

The second priority is to develop new disease models, both in the lab and within the patient population. Additionally, efforts must be made to investigate and categorize the range of symptoms and disease features. To date, no clinical or observational trials have been conducted on MPAN, so we lack comprehensive data describing symptoms and outcomes. Finally, researchers need to determine which tissues are likely to be affected by mutations to C19orf12.

Basic research can provide the foundation for insights with the potential for therapeutic interventions in MPAN. No drug or therapy has yet been found to modify MPAN. In theory, gene therapy offers promise, but at this stage, it is only a concept. Research may uncover the benefit of other drugs, including ones now used for other diseases.

Overall, the consensus from the roadmap highlights the need for translational research, which bridges scientists, clinicians and patients together. It allows for basic research to be more quickly translated into practical applications for patients, a priority identified in the strategic planning process.

We are hopeful that our knowledge of MPAN will grow, and that there will be help for MPAN families who have been waiting for years to see a breakthrough in research and potential treatments.




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