NBIA NEWS & INFORMATION

April 2022

By Patricia Wood

San Francisco-based CoA Therapeutics reports that it has successfully completed the Phase I study of healthy volunteers for a potential drug compound for Pantothenate Kinase-Associated Neurodegeneration (PKAN).

The Phase 1 trial of BBP 671 examined the safety, tolerability and effects of the drug on healthy volunteers, such as absorption rate, effect on metabolism, how it is excreted and how it is distributed throughout the body. The goal was to not only assess the drug’s safety but to determine a suitable dose and identify any potential problems before advancing to testing in PKAN individuals.

The company will present its findings at the 4th Pan American Parkinson’s Disease and Movement Disorders Congress, May 26 to 28, in Miami, Florida. CoA Therapeutics also will share study results later this year with our community, in addition to informing other scientists, clinicians and companies working on PKAN therapies.

The NBIA Disorders Association and several other NBIA patient organizations helped CoA Therapeutics develop an anonymous survey of PKAN individuals for assessing the compound’s effects when it moves to testing in affected individuals. Survey participants gave feedback on cognitive abilities, physical limitations, performance of daily activities and impact of travel. In all, 183 surveys from 23 countries were completed. Based on that feedback, the company decided to use the drug in small tablet form for the PKAN trial. (You can read a summary of the survey results here).

CoA Therapeutics says the company is focused on two activities this year: improving the formulation of compound BBP-671 and getting feedback on the clinical trial design from regulators in the European Union (European Medicines Agency) and the United States (Food and Drug Administration). Company officials will meet with regulatory authorities later this year and hope to have clinical sites open in the US and Europe by mid-2023. Anna Wade, vice-president of operations said, “We appreciate that time is of the essence for individuals with PKAN and their families, and we are moving as fast as possible.”

April 2022

Dr. Young Ah Seo from the University of Michigan School of Public Health in Ann Arbor, Michigan.

A University of Michigan researcher was awarded a new grant to continue her work into seeking potential treatments for BPAN, now the most common form of NBIA.

Dr. Young-Ah Seo received a one-year grant of $66,366 from the annual Million Dollar Bike Ride. Money raised by NBIA families and friends was matched up to $30,000 by the University of Pennsylvania Orphan Disease Center.

“The overall goal of this project is to develop new therapeutic strategies that can reduce brain iron overload and iron-induced neurodegeneration in BPAN patients,” Seo says. “We previously identified that a naturally occurring small molecule is exceptionally effective at promoting iron mobilization.”

The goal now is to use cell models derived from BPAN individuals to test whether that small molecule can be used to stave off the damage the disorder causes.

Seo completed a study in August 2021, “Defining the Roles of Iron in BPAN,” after receiving a first-ever early-career research grant from the NBIA Disorders Association for $150,000 in 2018.

That study’s objective was to identify the key proteins and pathways that are associated with the brain’s iron accumulation when the WDR45 gene is deficient in individuals with Beta-propeller protein-associated neurodegeneration. The study also examined how neurodegeneration is affected by the altered iron uptake and metabolism.

Seo’s team created a cell model of BPAN without the WDR45 gene, which showed increased levels of iron, suggesting it accurately reflected the condition seen in individuals with BPAN.

Additionally, they observed that the accumulation of iron within the model was linked to an impairment in the process that aims to prevent a dangerous amount of iron from being stored in the brain. Lastly, the deficiency in the WDR45 gene’s protein led to an excess of iron in the mitochondria, altered the mitochondrial metabolism and caused overproduction of toxic reactive oxygen species, which are highly reactive molecules that can lead to cell damage.

The findings of the first study have been published in the Journal of Neurochemistry, titled "A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation."

Seo’s Million Dollar Bike Ride-funded research, titled “Reversing Brain Iron Overload in BPAN by a Natural Small Molecule,” continues the work of the prior grant and aims to develop new therapeutic strategies that can reduce the iron accumulation in the brain and the resulting neurodegeneration in patients with BPAN.

Seo says that she is “very happy to be awarded the BPAN grant,” and is “looking forward to working on this project.” She also says that she plans to apply for a federal grant from the National Institutes of Health to further that research. First, however, she says she needs to wait on “more preliminary data from BPAN animal models as well as the preliminary data from this new grant.”

 

 

April 2022

Amber Denton of Houston is the new vice president of the NBIA Disorders Association.

The NBIA Disorders Association Board of Trustees has elected Amber Denton of Houston to be its new vice president. She is a prolific fundraiser for the organization, chair of the board’s Development Committee and the mother of a daughter with BPAN.

Denton, an instructional specialist in an elementary school, joined the board in fall 2019. She has been raising awareness about NBIA and hosting community fundraising events to support the organization even before becoming a trustee. She helps plan and leads efforts for the organization’s major fundraising events, including Rare Disease Day, the Million Dollar Bike Ride and GivingTuesday.

When her daughter, Sydney, was diagnosed with BPAN, she wrote a book, Sydney’s Song, that described how her daughter communicates with song instead of words.

Matthew Ritzman, board of trustees chair, says that Denton is “considerate, dedicated, organized, respectful and thoughtful. … At every turn she has devoted increasing efforts to our cause. There is nobody in or out of the organization that is better fit for the position of VP than Amber.”

Mary Ann Roser of Austin, former vice president.

Denton succeeds Mary Ann Roser as vice president. Roser joined the board in 1998 and has helped with the newsletter and other writing and editing for the organization.

She stepped down from the board Dec. 31, 2021, but continues to volunteer and edit the newsletter.

Ritzman expressed gratitude for Roser’s work over the years. “I always appreciated [her] commitment to the NBIA Disorders Association” and how she “helped establish the very foundation of this organization and kept us focused,” he said. “I will miss her wit, tenacity, transparency and boldness in our planning and board meetings.”