Molecular mechanisms of cell death in Choroideremia

Choroideremia (CHM) is a progressive retinal degenerative disorder that currently lacks effective treatments, affecting approximately 1 in 2,000 people worldwide. Although gene supplementation is the most advanced clinical strategy, a recent Phase 3 trial failed to meet its primary and secondary endpoints. A key limitation of this study was the inclusion of older patients, whose extensive retinal degeneration reduced the potential therapeutic benefit. Moreover, the inherent fragility of aged retinal tissue contributed to surgical complications and heightened local inflammatory responses.

Given these challenges, there is a critical need to explore complementary approaches that may slow disease progression and/or mitigate inflammatory responses associated with current interventions. However, the mechanisms driving degeneration in CHM remain poorly understood. 

In this project, we aim to elucidate the molecular pathways underlying the degenerative and inflammatory processes in CHM. As an initial screening step, we will employ mass spectrometry-based proteomics to perform a comprehensive analysis of stem cell-derived retinal pigment epithelium (RPE) cells from CHM patients. The most promising targets will then be validated in our mouse model of CHM.  



Period: 2022 - Ongoing

Funding: