Dr. Wenzhen Duan, M.D., Ph.D., M.S.
Director, Translational Neurobiology Laboratory
Dr. Wenzhen Duan, M.D., Ph.D, Professor of Psychiatry and Director of Laboratory of Translational Neurobiology at Johns Hopkins University School of Medicine. The bottleneck to wide-spread application of gene therapy for Huntington’s disease (HD) relates to the delivery by crossing the blood brain barrier and or reach to the brain regions most affected in HD. Wenzhen and her team are developing brain penetrable lipid-based nanoparticles (LNPs) for the safe delivery of gene therapies. LNPs are efficient in delivering therapeutic agents to the brain and are currently the lead non-viral delivery systems for enabling the clinical potential of genetic drugs. The project is aimed to provide fundamental knowledge and a proof-of-principle for safe delivery of a powerful gene therapy to treat HD.
Dr. Myriam Heiman
Our project has been focusing on a novel gene therapy approach for Huntington’s disease (HD). In HD, dysfunction of the cerebrovasculature and the associated breakdown of the blood-brain barrier (BBB) have been observed in early stages of the disease. We proposed that targeting the cerebrovasculature itself with a viral gene therapy would be restorative and potentially halt disease progression. We’ve been using this approach in the past year and have observed great potential in delaying disease progression within animal models of HD. We are now characterizing these changes extensively at cellular, molecular, and behavioral levels and are complementing these animal studies with high-resolution molecular profiling in the human HD cerebrovasculature. We are planning to prepare a manuscript for publication in the coming year.
Dr. Michael Hayden
October 18, 2023 Preclinical evaluation of modulating post-translational palmitoylation to treat Huntington disease Palmitoylation is an important post-translational modification that plays a key role in protein trafficking and stability. We have previously shown that palmitoylation of the mutant huntingtin (mHTT) protein is reduced in Huntington disease (HD), and that mHTT made resistant to this modification leads to increased mHTT aggregation and cell death. These findings have suggested a potential link between palmitoylation defects and neurodegeneration in HD. Recent studies from our group and others have demonstrated that enhancing palmitoylation of mHTT using small molecules is neuroprotective in cell and animal models of Huntington disease. Therefore, modulating palmitoylation levels of mHTT may represent a promising approach to treating HD, with efforts to develop and test such therapies in early clinical development. With this grant, we have built on our previous work characterizing the impact of mHTT palmitoylation on disease-related phenotypes in neurons derived from HD mutation carriers. We are very grateful for continued support of the Bev Hartig Huntington’s Disease Foundation as we continue to explore ways to treat this devastating disease.
Summerfield Health Care Center
Summerfield Health Care Center in Cloverdale, Indiana is one of four specialty communities in the country caring for residents with Huntington’s Disease. In 2022, the foundation awarded $5,590 to the facility to purchase two Carefoam chairs. These chairs offer restraint-free comfort and portability allowing residents in advanced stages of the disease to remain socially engaged in the activities provided by the community.