Physician's Corner

A one-time treatment approach using adeno-associated virus (AAV) vectors to deliver healthy genetic material to cells. This research aims to silence or replace the mutated TUBB4A gene causing H-ABC and has shown promising results in similar leukodystrophies.

View more HERE about the AAV Gene Therapy

Each year, an estimated 18,000 babies are born with some form of leukodystrophy, a group of rare genetic disorders that affect the brain’s white matter.

Of these, approximately 1,650 are believed to be TUBB4A‑related, based on current diagnostic rates.

To date, just over 200 individuals worldwide have been confirmed to have a TUBB4A mutation—but many more may remain undiagnosed.

Why this matters for treatment:
Because TUBB4A leukodystrophy is rare, progressive, and currently incurable, the small patient population makes traditional drug development very slow. That’s why Foundation to Fight H‑ABC is focused on accelerating antisense oligonucleotide (ASO) therapy, a promising targeted approach already being studied for other ultra‑rare neurological diseases.

ASO research is underway now, with the goal of slowing or stopping disease progression for children and adults living with TUBB4A leukodystrophy.

Link to information on: ASO Treatment

Sources:
• Vanderver A. et al. (2021). The leukodystrophies: Clinical and genetic update. Nature Reviews Neurology.
• Hunter A. et al. (2022). Prevalence estimates from leukodystrophy registries. Journal of Rare Disorders.

RARE-X is a nonprofit platform for collecting, structuring and sharing rare disease data. We partner with patient advocacy groups to make data collection accessible and easy for rare disease communities — and ensure that the data is high quality and ready to be used to accelerate research and drive forward urgently needed treatments.

Link to:
Rare-X Research Program

Molecular Genetics and Metabolism 144 (2025) 109048

Advancing H-ABC Research Through Drug Repurposing

Drug repurposing offers a promising and pragmatic approach to accelerate treatment options for patients with H-ABC/TUBB4A-related leukodystrophy. In partnership with an AI-enabled biotech company, the Foundation to Fight H-ABC is supporting an early-stage initiative that leverages transcriptomic analysis to identify existing FDA-approved compounds with potential therapeutic benefit. This effort is not a clinical trial, but a preclinical precision-matching study that requires RNA samples from affected individuals and a genetically matched control (same-sex biological parent). We welcome collaboration with providers and clinical researchers to help identify eligible families, facilitate sample collection, and interpret results that may inform individualized or population-level next steps.

bioRxiv: Therapeutic suppression of Tubb4a rescues H-ABC leukodystrophy (2024)

Data Report: A novel TUBB4A mutation G96R identified in a patient…(2017)

eLife: TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model (2019)

Patient Listening Sessions can either be FDA-requested (where FDA has a specific set of questions to ask) or patient-led (when a patient community wants to share their perspectives with the FDA). Only the FDA, patients, caregivers, and advocates participate in the session.

H-ABC Session

FDA Patient Listening Session Summaries

UMass Chan Medical School Horae Gene Therapy Center: The Faculty of the Horae Gene Therapy Center is dedicated to develop therapeutic approaches for rare inherited disease for which there is no cure. We utilize state of the art technologies to either edit mutated genes that produce disease-causing proteins or introduce a healthy copy of a gene if the mutation results in a non-functional protein.

Children’s Hospital of Philadelphia: The Leukodystrophy Center at CHOP includes a broad team of specialists dedicated to providing care, testing and treatments to infants and children with inherited white matter diseases.

Adeline Vanderver, MD. Program Director of the Leukodystrophy Center, and Jacob A. Kamens Endowed Chair in Neurologic Disorders and Translational Neurotherapeutics at Children's Hospital of Philadelphia.

Global Leukdystrophy Initiative - Clinical Trial Network: The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) is a consortium of scientists, industry stakeholders, and patient advocacy leaders working together to promote advances in the diagnosis and treatment of leukodystrophies.

A Career Devoted to the Battle Against Deadly Brain Disease - Marjo van der Knaap