The Bev Hartig Huntington’s Disease Foundation (TBHHDF) strives to seek out cutting-edge research that would not be funded without the Foundation that Bev inspired. TBHHDF collaborates with The CHDI Foundation, a non-profit biomedical foundation whose aim is to rapidly discover and develop drugs that retard the progression of HD, and to identify up-and-coming researchers with promising studies.
To date, $3.3 million has been awarded by TBHHDF to specific research seeking to develop a cure for Huntington’s Disease.
Below are the most recent Grant Recipients, individually selected by the TBHHDF board based on their focus to study the brain and how to slow the CAG-repeaters, which is a key indicator for Huntington’s Disease.
2024 Recipients
Dr. Wenzhen Duan, M.D., Ph.D. – $162,691
Professor of Psychiatry and Neuroscience
Director, Laboratory of Translational Neurobiology
Co-Director, Division of Neurobiology
Johns Hopkins University School of Medicine
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin (HTT) gene, leading to the production of mutant huntingtin protein. A promising therapeutic approach involves eliminating the mutant RNA transcripts to mitigate these effects. The U1 small nuclear RNA (U1 snRNA), a component of the spliceosome, has been identified as a potential tool for inhibiting target gene expression, offering a novel strategy for reducing mutant HTT levels. However, delivering gene therapies to the brain is challenging due to the blood-brain barrier (BBB). Recent advancements in magnetic resonance-guided focused ultrasound (FUS), combined with microbubble agents have shown potential in temporarily disrupting the BBB, allowing for targeted delivery of therapeutics to specific brain regions. This project proposes developing a clinically scalable method using FUS and microbubble conjugates to deliver U1 snRNA to the brains of HD mice, aiming to establish a foundation for future clinical applications.
Dr. Myriam Heiman – $100,000
It is known that the cerebrovasculature and the blood-brain barrier (BBB) it creates become dysfunctional in Huntington’s disease (HD), often years before other HD symptom onset. Previous work in the field has shown that mutant huntingtin can be found within the brain vasculature of HD patient tissue and HD model mice, and can lead to the disruption of BBB properties. With the Foundation’s support, we have been using an adeno-associated virus (AAV) targeting approach for gene therapy of the BBB in HD mouse models, targeting key cerebrovascular genes involved in or affected in HD. Our results in mice show that this approach has great promise to modulate HD symptom progression, and since these viral tools are delivered as a one-time blood (intravenous) injection, bypass any adverse effects in neurons, they in principle could be safely applicable to human patients as well.
2023 Recipients
Dr. Wenzhen Duan – $146,112
Preclinical development of mutant huntingtin targeting therapeutic strategies
Our recent preclinical data demonstrates the efficacy of an expanded CAG gRNA guided CRISPR/Cas13d system in reducing mutant HTT mRNA and protein levels, while preserving normal HTT levels in Huntington’s disease (HD) patient cell models and a knock-in mouse model. This experimental treatment successfully addresses motor deficits and neuropathology in HD mice, as well as reverses HD-related transcriptomes in human HD iPSC-derived striatal neurons and HD mouse brain. CRISPR/Cas13d serves as a proof-of-concept for lowering mutant HTT. However, a significant challenge lies in the collateral RNA cleavage feature, posing potential off-target side effects. In this project, we aim to address challenges of collateral RNA cleavage and explore alternative RNA-targeting approaches for HD therapy. Completion of the proposed studies will provide a foundation that potentially allows for clinical consideration of novel mutant HTT allele-selective RNA silencing strategies for treating this devastating disease. We are grateful for the continued support of the Bev Hartig Huntington’s Disease Foundation.
IU Social Worker – Center for Excellence – $20,000
Summerfield – $5,000
Dr. Miriam Heiman – $100,000
HDSA Human Biology Project – Dr. Roy Maimon PhD – $75,000
Learn More
What is Huntington’s Disease?
Huntington’s Disease is a degenerative brain disease that strikes in mid-life, usually between the ages of 30-40. People lose their ability to walk, talk, and even feed themselves. Even though people may live for 10-20 years with this disease, their quality of life is taken from them.
Who Was Bev Hartig?
In 1998, about one year after getting married, Bev received a paralyzing phone call that her birth father had been diagnosed with HD. This meant every sibling had a 50% chance of inheriting this disease. She found out that she also carried the gene and would suffer the same tragic fate.