Dr. Wenzhen Duan – $146,112
Preclinical development of mutant Huntington 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
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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.