How lysine breakdown is controlled in glutaric aciduria type 1 (GA1)
Allosteric regulation of lysine degradation as a novel pathophysiological mechanism in glutaric aciduria type 1
This project looks at whether changes in how the body controls lysine breakdown cause toxic metabolite buildup in people with glutaric aciduria type 1 (GA1).
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11173878 on NIH RePORTER |
What this research studies
If I or my child joined, the team would examine the molecular switches that control lysine degradation to understand why harmful acids build up in GA1. They will use patient-derived samples, cell lines, and a GA1 mouse model to study enzyme control points called allosteric sites. The researchers aim to pinpoint how loss of the GCDH enzyme leads to neurotoxic metabolites and which steps might be targeted by new therapies. Findings could guide drug development beyond current dietary and supplement approaches.
Who could benefit from this research
Good fit: People diagnosed with GA1 (including those identified by newborn screening) and their caregivers, especially those willing to provide clinical information or biological samples, would be the most relevant participants.
Not a fit: People without GA1 or those seeking an immediate treatment are unlikely to receive direct clinical benefit from this mechanistic research.
Why it matters
Potential benefit: If successful, this work could reveal new drug targets to reduce toxic organic acids and help prevent neurological damage in people with GA1.
How similar studies have performed: Allosteric regulation has produced useful targets in other metabolic disorders, but applying this approach specifically to GA1 is relatively new and not yet proven as a therapy.
Where this research is happening
New York, United States
- Icahn School of Medicine at Mount Sinai — New York, United States (Active)
Researchers
- Principal investigator: Houten, Sander Michel — Icahn School of Medicine at Mount Sinai
- Study coordinator: Houten, Sander Michel
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.