Finding the harmful forms of the huntingtin protein
Characterizing the Conformations and Neurotoxic Species of Huntingtin
['FUNDING_R01'] · UNIVERSITY OF SOUTHERN CALIFORNIA · NIH-11138543
This project looks for the specific harmful shapes of the mutant huntingtin protein that damage brain cells in people with Huntington's disease and for antibodies that stick to those shapes.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF SOUTHERN CALIFORNIA (nih funded) |
| Locations | 1 site (Los Angeles, UNITED STATES) |
| Trial ID | NIH-11138543 on ClinicalTrials.gov |
What this research studies
Researchers will make very pure versions of the mutant huntingtin exon-1 protein and create libraries of monoclonal antibodies that recognize different assemblies. They will use biochemical and biophysical tests to see which antibodies bind which protein shapes and whether binding changes how the protein misfolds, seeds, or aggregates. The team will use human neuron models to observe which protein forms enter neurons and cause damage, and will determine structures with methods such as Cryo-EM and map neuronal receptors involved in entry. This work is laboratory and cell-based and aims to reveal targets for future diagnostics or treatments rather than testing therapies in people now.
Who could benefit from this research
Good fit: People with Huntington's disease or individuals who carry the HD gene mutation would be most relevant to this work and to any future trials that build on it.
Not a fit: People without Huntington's disease or those with unrelated neurological conditions are unlikely to benefit directly from this laboratory-focused work.
Why it matters
Potential benefit: If successful, this work could identify the toxic huntingtin species and antibody targets that lead to new diagnostics or antibody-based treatments for Huntington's disease.
How similar studies have performed: Previous studies have shown huntingtin fragments can form toxic aggregates and that some antibodies bind aggregates, but precisely mapping pathogenic conformations and targeting them with high-specificity, structure-specific antibodies is still largely novel.
Where this research is happening
Los Angeles, UNITED STATES
- UNIVERSITY OF SOUTHERN CALIFORNIA — Los Angeles, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: KHOSHNAN, ALI — UNIVERSITY OF SOUTHERN CALIFORNIA
- Study coordinator: KHOSHNAN, ALI
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.