Drug Repurposing: A Faster Path to H-ABC Treatment

Thank You for Helping Us Take the Next Step Toward Treatment

We’ve completed recruitment for our drug repurposing study—thanks to the incredible families who participated.

Every family's contribution brings us closer to understanding this disease and identifying treatments that could slow or improve its progression. Together, we are moving this research forward—with urgency and hope.

What Is Drug Repurposing?

Also known as drug repositioning, drug repurposing involves finding new medical uses for drugs that are already approved or in development. Because these drugs have already passed many safety and toxicity tests, repurposing them can accelerate development and reduce costs, offering faster access to potential treatments—especially important for rare diseases like H-ABC.

Key Aspects of Drug Repurposing

  • Some drugs have secondary effects that make them useful for unrelated conditions.
    Example: Sildenafil (Viagra) was originally developed for hypertension and later repurposed for erectile dysfunction.

  • Advanced computational platforms can scan genetic data, drug databases, and disease pathways to identify promising candidates.

  • Off-label drug use by doctors can reveal new therapeutic potential. Physicians can legally prescribe approved drugs for alternative uses if medically appropriate.

  • Drugs can be evaluated in new disease models (in vitro or in vivo).
    We have access to H-ABC mouse models to support this testing.

  • Repurposed drugs may also be used alongside others for enhanced effect.

Why Drug Repurposing Matters

For rare conditions like H-ABC, traditional drug development can be slow, costly, and often overlooked by large pharmaceutical companies. Drug repurposing offers a powerful alternative—one that brings real hope to families waiting for answers.

Here’s why it matters:

  • Faster Development – Approved drugs can move into clinical trials much sooner, accelerating the path to treatment.

  • Lower Costs – Because safety data already exists, development is more affordable and efficient.

  • Real Hope for Rare Diseases – For conditions like H-ABC that don’t attract large-scale investment, repurposing offers a realistic and urgent path forward.

By participating in this study, families have the opportunity to help drive meaningful progress—possibly years ahead of traditional timelines.

Our Drug Repurposing Partnership

The Foundation to Fight H-ABC/TUBB4A has partnered with an AI-enabled biotech company that specializes in drug repurposing for complex diseases. Their cutting-edge platform integrates:

💻 Advanced computational drug matching

🧪 Preclinical screening of promising compounds

🧬 Patient stratification using real-world genetic data

This innovative approach helps identify existing drugs or compounds that may slow or manage symptoms of H-ABC / TUBB4A-related leukodystrophy—potentially shortening the timeline to treatment.

What They Needed from Families

To power this research, the team collected RNA samples from:

  • 20 individuals diagnosed with H-ABC

  • One same-sex biological parent per participant (used as a genetic control)

✅ A simple, non-invasive nasal swab was used

🌍 Participation was open to families worldwide

Consent & Precision

Participants were also asked to complete a few short forms, including one that gave permission for their genetic data to be compared to that of a genetically similar—but unaffected—individual. This comparison improves the precision of the analysis and helps identify the most promising treatment targets.

Drug Repurposing Initiative: Moving Toward Treatment

We’ve completed a major milestone in our drug repurposing effort: testing and sample collection are now complete.

This isn’t yet a cure—but it’s a critical step toward identifying treatments that may help manage or slow the symptoms of H-ABC / TUBB4A-related leukodystrophy. The goal is to find:

💊 An existing drug that a physician may be able to prescribe off-label
🔬 Or a promising compound that could be further developed for H-ABC, potentially speeding up future clinical trials

Clinical experts are guiding every step to ensure accurate interpretation and meaningful next steps.

Where We Are Now?

  • Recruitment of 20 families is now complete

  • Samples were sent to our biotech partner for detailed analysis.

  • The analysis process took approximately a month.

  • Results have been received and will be reviewed by our scientific advisors.

Computational Drug Repurposing Study Findings for H-ABC (TUBB4A-Related Leukodystrophy)

The Foundation to Fight H-ABC partnered with Unravel Biosciences to conduct a computational systems biology study using patient-derived molecular data from individuals with TUBB4A-related leukodystrophy. This work was designed to explore the molecular pathways underlying the disease and identifying potential therapeutic opportunities.  These findings were recently presented in a webinar to the patient community.  See attached link to the webinar.

Unlike traditional drug discovery, which often begins by targeting a single gene or protein, Unravel's platform analyzes global patterns of gene expression (the transcriptome) from patient samples. Using artificial intelligence and network-based computational modeling, these disease-associated molecular signatures are compared with the known biological effects of thousands of FDA-approved and investigational compounds. The goal is to identify existing medications that may help normalize disease-associated biological pathways and prioritize them for further research.

The study analyzed samples from 18 individuals with H-ABC and identified two transcriptomically distinct molecular subgroups within this study cohort. One subgroup consisted predominantly of individuals carrying the p.Asp249Asn (D249N) variant, while the second represented a more genetically diverse group. These findings suggest that although patients share the same diagnosis, there may be important biological differences that could ultimately influence therapeutic response.

One of the most significant findings was the consistent prioritization of calcitriol, the active prescription form of vitamin D, across both molecular subgroups. The computational analysis suggested that activation of the vitamin D receptor (VDR) may beneficially influence disease-associated molecular signatures observed in H-ABC, making calcitriol an attractive candidate for further translational research. Importantly, this finding relates to VDR signaling and should not be interpreted to mean that over-the-counter vitamin D supplementation would produce the same biological effects.

These findings do not demonstrate that calcitriol or any other medication is an effective treatment for H-ABC. Instead, they provide scientifically prioritized hypotheses that require laboratory validation and carefully designed clinical studies. The Foundation believes these results represent an important step toward a more precise, biology-driven approach to therapy development.

Moving forward, the Foundation hopes to collaborate with leading academic and clinical partners—including CHOP—to validate these findings through laboratory studies, biomarker research, and prospective clinical investigations. By combining clinical expertise with advanced computational biology, patient-derived molecular data, and translational research, we hope to accelerate the discovery of safe and effective therapies for individuals living with H-ABC.

FAQ: Unravel Bio Computational Drug Repurposing Study

Important Disclaimer

The Unravel Biosciences study generated computational predictions designed to prioritize future research. These findings are hypothesis-generating and have not been validated in laboratory or clinical studies. The Foundation is not recommending the off-label use of calcitriol or any other medication. Families should consult their healthcare providers before making any treatment decisions.