Lowering MSH3 as a potential way to slow Huntington's disease
High-throughput small molecule screen to reduce endogenous level of Msh3 for disease-modifying HD therapy
['FUNDING_OTHER'] · UNIVERSITY OF CALIFORNIA LOS ANGELES · NIH-11261766
This project tries to find small drug-like molecules that reduce the MSH3 protein as a possible way to slow Huntington's disease in people with the HTT gene mutation.
Quick facts
| Phase | ['FUNDING_OTHER'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF CALIFORNIA LOS ANGELES (nih funded) |
| Locations | 1 site (LOS ANGELES, UNITED STATES) |
| Trial ID | NIH-11261766 on ClinicalTrials.gov |
What this research studies
Researchers are using a new mouse-derived reporter that lights up with Msh3 to screen large libraries of small molecules in cells to find compounds that lower endogenous Msh3 levels. Promising hits from the primary mouse embryonic fibroblast assay will be retested in human cell lines and in primary striatal neurons, the brain cell type most affected in Huntington's disease. Secondary assays will measure MSH3 RNA and protein directly and remove compounds that are toxic or act through undesirable mechanisms. The R61 phase is focused on proving the screening pipeline is scalable and reproducible and on prioritizing the best candidate molecules for further preclinical development.
Who could benefit from this research
Good fit: People with Huntington's disease caused by a CAG-repeat expansion in the HTT gene would be the eventual candidates for therapies developed from this work and for future clinical trials.
Not a fit: Because this is early, preclinical screening work, people without the HTT mutation or those seeking immediate treatment are unlikely to benefit now.
Why it matters
Potential benefit: If successful, this work could identify drug leads that reduce mutant huntingtin aggregation and slow disease progression in people with Huntington's disease.
How similar studies have performed: Mouse genetic studies showed that lowering Msh3 reduces mutant huntingtin aggregates and improves molecular signs of disease, but small-molecule MSH3-lowering approaches are new and have not yet been proven in humans.
Where this research is happening
LOS ANGELES, UNITED STATES
- UNIVERSITY OF CALIFORNIA LOS ANGELES — LOS ANGELES, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: YANG, XIANGDONG WILLIAM — UNIVERSITY OF CALIFORNIA LOS ANGELES
- Study coordinator: YANG, XIANGDONG WILLIAM
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.