Small-molecule approach to lower huntingtin in Huntington's disease
Understanding small molecule modulation of splicing for Huntington's disease therapy
This research explores whether brain-penetrant small drugs can change how the huntingtin gene is read to reduce toxic huntingtin protein for people with Huntington's disease.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Colorado Denver NIH-funded |
| Lab location | 1 site (Aurora, UNITED STATES) |
| Project ID | NIH-11303401 on NIH RePORTER |
What this research studies
Researchers will study how small-molecule splicing modulators cause the huntingtin (HTT) gene to include a “poison” exon so the mutant HTT mRNA is degraded. They will compare different chemical classes and measure effects on RNA, protein levels, and CNS delivery using cell models and human-derived samples and relevant preclinical systems. The team will also look for molecular signals linked to peripheral nerve toxicity so safer compounds can be designed. This work is lab-focused and aims to guide development of drugs that could later enter clinical trials rather than enrolling patients now.
Who could benefit from this research
Good fit: People with a confirmed Huntington's disease mutation or carriers would be the eventual candidates for therapies developed from this work, though this grant itself focuses on laboratory research rather than a clinical trial.
Not a fit: People without the HD mutation and those seeking immediate symptom relief are unlikely to benefit directly from this preclinical project.
Why it matters
Potential benefit: If successful, this work could lead to safer, orally available drugs that lower huntingtin and potentially slow or stop Huntington's disease progression.
How similar studies have performed: Related small-molecule splicing drugs have succeeded in spinal muscular atrophy (risdiplam) and have shown mixed results in HD (branaplam halted for toxicity, other analogs in phase 2), so the approach is promising but still needs safety and delivery improvements.
Where this research is happening
Aurora, UNITED STATES
- University of Colorado Denver — Aurora, United States (Active)
Researchers
- Principal investigator: Zhao, Rui — University of Colorado Denver
- Study coordinator: Zhao, Rui
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.