How genes shape Lewy body disease at different stages
Project IV: In Vivo Dissection of Genetic Modifiers on Different Stages of Synucleinopathy
['FUNDING_P01'] · UNIVERSITY OF PENNSYLVANIA · NIH-11184467
Researchers are looking at how different genes change the timing and spread of alpha‑synuclein (Lewy body) pathology in people with Lewy body disorders and Alzheimer's disease.
Quick facts
| Phase | ['FUNDING_P01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF PENNSYLVANIA (nih funded) |
| Locations | 1 site (PHILADELPHIA, UNITED STATES) |
| Trial ID | NIH-11184467 on ClinicalTrials.gov |
What this research studies
This project combines experiments in living models with analysis of human brain and tissue samples to see how genetic risk factors change alpha‑synuclein (aSyn) pathology. Scientists will focus on endo‑lysosomal risk genes such as TMEM175 and GPNMB and compare their effects during early (prodromal) and advanced stages of disease. They will map where Lewy bodies and neurites appear across the central, peripheral, and enteric nervous systems and test how different genes make those patterns worse or milder. Results come from lab experiments, genetic manipulations in vivo, and analysis of autopsy tissues rather than immediate patient treatments.
Who could benefit from this research
Good fit: People diagnosed with Lewy body dementia, Parkinson's disease, or Alzheimer's disease, or individuals willing to donate brain tissue after death, would be most relevant to this work.
Not a fit: People without alpha‑synuclein pathology or those seeking an immediate change in clinical care are unlikely to receive direct benefits from this research.
Why it matters
Potential benefit: If successful, this work could reveal genetic mechanisms that explain symptom differences and point to new targets for therapies to slow or prevent Lewy‑body related decline.
How similar studies have performed: Prior work from the team showed that TMEM175 and GPNMB affect aSyn pathology, so this project builds on those findings while expanding to many other risk genes and disease stages.
Where this research is happening
PHILADELPHIA, UNITED STATES
- UNIVERSITY OF PENNSYLVANIA — PHILADELPHIA, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: LUK, KELVIN C — UNIVERSITY OF PENNSYLVANIA
- Study coordinator: LUK, KELVIN C
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.
Conditions: Alzheimer's disease patient