Research
funding critical research: Supporting Doctors and Scientists in the Quest for a Cure
With support from generous donors like you, the Foundation to Fight H-ABC funds academic institutions, children’s hospitals, and research scientists that are developing cutting-edge genetic-based treatments for children with H-ABC / TUBB4A-related leukodystrophy that will ultimately not only save their lives, but will also restore their capabilities.
To date, the Foundation to Fight H-ABC has raised approximately $100,000 a year for H-ABC disease research. With your help, we will continue providing these dedicated doctors and scientists with the funding they need to develop treatments and find a cure. Progress is being made, and pathways to treatments are within sight.
Why GRASS-ROOTS Funding for H-ABC Research Is so Important
H-ABC is a rare disease, and it’s given neither the attention nor resources it needs. As there is little interest in funding the research from pharmaceutical companies or academic institutions at this stage in the research, it’s up to us to move the research forward by finding the funding on our own. Our foundation seeks grants from institutions, donations from corporations, supports fund raising efforts by hospitals, and, most importantly, raises funds through the grass-roots efforts of our friends and family.
The donations we receive are used for a variety of purposes: funding the work of those conducting genetic research, helping to cover the related costs of research, establishing facilities where doctors can study longitudinal patient data, and more. All donations go directly to our research partners.
With each dollar allocated to H-ABC disease research, we get one step closer to entering the clinical trial phase and finding a cure—one that children with H-ABC so desperately need.
What a Cure for H-ABC May Look Like
According to researchers, there are currently three possible approaches to treating H-ABC:
Antisense Oligonucleotides (ASO): 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 (AVV) vectors: 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 AVV vectors in Nature: Adeno-associated virus vector as a platform for gene therapy delivery; Nature Reviews Drug Discovery; by Dan Wang, Phillip W. L. Tai & Guangping Gao; February 1, 2019.
CRISPER Mediated Correction: Correct the mistake in the TUBB4A tubulin gene itself through a highly novel gene-editing approach called CRISPER 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.
Previous Projects that the
foundation to fight h-abc has helped fund:
2017-2018
In addition to general research at CHOP, the Foundation has also contributed to the intial roll out of the H-ABC Natural History Study: This is an ongoing study which 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. See News and Articles for most recent updates
Funded H-ABC Scientific Conference held at Children’s Hospital of Philadelphia.
2018-2019
Yale Mice discovery and knockdown model
Contributed to H-ABC Family Conference held at Children’s Hospital of Philadelphia
2020
Translational research at CHOP for ASO mice model
Launch of the Two-Year Sponsored Research Agreement with UMass for AAV research; Extended through 2025.
2022
March 2022. Launch of the Patient Database
May 2022. FDA Listening Session, to educate the FDA and researchers globally about H-ABC
How H-ABC Disease Research Has Progressed
Although the path to a cure is a difficult one, a significant amount of progress has been made on H-ABC disease research already.
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) is 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.
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.
Perform cellular-level research of the disease - COMPLETE
Research biological makeup of the disease - COMPLETE
Determine best approach for gene therapy - IN PROGRESS
Get FDA approval for clinical trial
Start clinical trial