Funding Critical Research

Supporting Doctors and Scientists
in the Quest for a Cure

With the support of generous donors like you, the Foundation to Fight H-ABC is funding academic institutions, children’s hospitals, and research scientists who are developing cutting-edge, genetics-based treatments for children affected by H-ABC / TUBB4A-related leukodystrophy. These treatments are designed not only to save lives, but to restore capabilities.

Average of $100,000 per year directed to research since 2015. With your help, we can continue fueling the science that brings us closer to a cure. Progress is being made, and pathways to treatment are within sight.

Why Grassroots Funding for H-ABC
Research Is So Important

H-ABC is a rare disease—and that means it receives neither the attention nor resources it needs.

As there is little investment from pharmaceutical companies or academic institutions at this stage of research, it’s up to us to move the science forward. Our Foundation applies for grants, seeks donations from corporations, supports hospital fundraising efforts, and—most importantly—relies on the grassroots support of families and friends like you.

Where Your Donations Go

Donations help:

  • Fund the work of researchers developing genetic therapies

  • Cover the high costs related to conducting and maintaining research

  • Establish and support facilities where doctors can study long-term patient data

  • Directly support our trusted hospital and university research partners

Every dollar we raise goes directly to H-ABC research.

With each dollar allocated to H-ABC research, we move one step closer to clinical trials—and to a future where children with H-ABC have access to life-changing treatments and, eventually, a cure.

What a Cure for H-ABC May Look Like

According to researchers, there are currently three possible approaches to treating H-ABC:

  • This ongoing treatment would reduce the expected toxicity to cells from the mutated tubulin by using an approach that captures the mutated RNA before it becomes a damaged protein.

    Read more about this in Nature: here.

  • Adeno-associated virus (AAV) vectors are the leading platform for gene delivery for the treatment of a variety of human diseases. Recent advances in developing clinically desirable AAV capsids, optimizing genome designs and harnessing revolutionary biotechnologies have contributed substantially to the growth of the gene therapy field. Preclinical and clinical successes in AAV-mediated gene replacement, gene silencing and gene editing have helped AAV gain popularity as the ideal therapeutic vector, with two AAV-based therapeutics gaining regulatory approval in Europe or the United States. Continued study of AAV biology and increased understanding of the associated therapeutic challenges and limitations will build the foundation for future clinical success. 

    Read more about AAV vectors in Nature here

  • Correct the mistake in the TUBB4A tubulin gene itself through a highly novel gene-editing approach called CRISPR that can correct ‘spelling mistakes’ in genes. CRISPR would correct the mutation at the DNA level in the TUBB4A gene.

    Read more about the first CRISPR therapy used directly in a person in Nature: here.

The ASO and AAV are more viable treatment options at this time and both are currently underway. The ASO will provide time for affected patient until a permanent cure is found using the AAV. We estimate the initial phase through clinical trials for each approach will cost approximately $5 million.

How H-ABC Disease Research

Has Progressed Over the Years

Although the path to a cure is a difficult one, a significant amount of progress has been made on H-ABC disease research already.

    • Supporting the CHOP Natural History Study: In addition to general research at CHOP, the Foundation has also contributed to the initial roll out of the H-ABC Natural History Study.

      This ongoing study is critical for gathering key data on patients in order to demonstrate the progression of the disease necessary for clinical trials. To date over 200 children are enrolled.

    • Funded H-ABC Scientific Conference held at Children’s Hospital of Philadelphia.

    • Building the Models Needed to Test Treatments
      Supported development and preservation of TUBB4A mouse models needed to study the disease and evaluate potential therapies. Yale Mice discovery and knockdown model

    • Bought H-ABC Researchers and Families Together
      Supported scientific and family conferences at CHOP to connect researchers, clinicians, and families and advance collaboration around H-ABC.

    • Supporting ASO Research at CHOP
      Supported CHOP research exploring antisense oligonucleotides as a potential strategy for reducing the effects of abnormal TUBB4A.

    • Launching AAV Gene Therapy Research with UMass Chan
      Initiated and funded a multi-year research program with UMass Chan and Yale to develop an AAV-based gene therapy approach for TUBB4A-related disease.

    • Launching the Patient Database
      Launched a patient database to help connect families, track disease progression, and prepare the community for future clinical trials.

    • Bringing the H-ABC Patient Voice to the FDA
      Organized an FDA Patient-Led Listening Session to communicate H-ABC disease progression, unmet needs, and what meaningful treatment would mean to families.

    • n-Lorem’s TUBB4A ASO Program
      H-ABC families donated patient cells and samples to support n-Lorem’s development of an experimental ASO treatment for TUBB4A-related disease.

    • First TUBB4A Patient Treated with an n-Lorem ASO
      Connor Gooley became the first child with a TUBB4A-related disorder to receive n-Lorem’s experimental ASO—marking the first treatment of a patient with a therapy targeting TUBB4A.

    • SynaptixBio Advances a Commercial TUBB4A ASO Program
      SynaptixBio advanced a separate commercial ASO program for TUBB4A-associated leukodystrophy, adding another potential disease-modifying approach to the therapeutic pipeline.

    • Launch of the Drug Repurposing Study with Unravel Bio
      Partnered with Unravel Bio to use patient RNA and computational analysis to identify existing drugs that could potentially be repurposed for H-ABC.

    • Patient RNA Identifies Potential Treatment Candidates - Drug Repurposing
      Analysis of samples contributed by H-ABC patients identified shared disease biology, patient subgroups, and potential drug candidates for further investigation.

    • Moving Drug Repurposing Toward Validation
      Began working with researchers and clinicians to determine how the strongest repurposing candidates could be validated through laboratory and clinical research.

    • Exploring Next-Generation CNS Drug Delivery

      Began engaging researchers around blood-brain-barrier and other emerging delivery technologies that could potentially improve how future H-ABC therapies reach the brain.

How We Got Where We are Today…

A timeline of scientific findings.

    • In 2002, Dr. Marjo S. van der Knaap identified H-ABC using magnetic resonance imaging (MRI), which has become a key part of detecting brain tissue patterns that are characteristic of the disease. 

  • In 2013, Dr. Marjo S. van der Knaap and others discovered that those affected by H-ABC carry a mutation in the TUBB4A gene, which makes a protein for microtubules. With genetic testing, doctors are now able to confirm changes in the TUBB4A gene and diagnose H-ABC.

  • In 2017, Dr. Ian Duncan concluded that H-ABC is the human counterpart of a neurological condition in rats. This rat model could serve as a testing ground for medications that inhibit microtubule formation.    

  • In 2021. Through the work of Professor Adeline Vanderver, Program Director of the Leukodystrophy Center of Excellence at Children’s Hospital of Philadelphia (CHOP) in the U.S, a gene therapy known as antisense oligonucleotides (ASOs) has been developed. SynaptixBio has recently entered into a research agreement with CHOP related to a new method for treating TUBB4A-associated leukodystrophy. Preclinical trial preparation is underway.

  • In 2024. Via N-1 individualized treatment protocol, the first child was treated with a novel ASO and to date is showing positive signs of efficacy and safety.

PATH TO A CURE

The steps below outline the path to a cure. The financial support provided by our donors and given directly to researchers has played an integral part in completing the first two steps.

Already, those who have made the choice to stand with us and fight have made a huge difference in the lives of those affected by H-ABC. 

  1. Perform cellular-level research of the disease - COMPLETE

  2. Research biological makeup of the disease - COMPLETE

  3. Determine best approach for gene therapy - IN PROGRESS

  4. Get FDA approval for clinical trial

  5. Start clinical trial

Join Our Fight TODAY

Help Fuel Cutting-Edge Research into a Cure Today!

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