Molecular mechanisms of cell death in Choroideremia

Choroideremia (CHM) is a progressive retinal degenerative disorder that remains incurable, affecting approximately 1 in 2,000 people worldwide. Although gene supplementation therapy is the most advanced clinical strategy, its recent phase 3 trial has failed to meet primary and secondary endpoints, underscoring the need for alternative approaches. One critical limitation of these trials has been the inclusion of older patients, whose extensive retinal degeneration compromises the sucess of gene therapies. Furthermore, the fragility of aged retinal tissue often leads to complications during surgical interventions and increased inflammatory responses. 

Given these challenges, it is essential to explore complementary methods that may prevent disease progression and/or moderate inflammatory reactions associated with current interventions. However, the mechanisms driving degeneration in CHM remain poorly understood, hindering the development of effective therapeutic strategies. 

In this project, we aim to elucidate the main pathways involved in the degenerative and inflammatory processes underlying CHM. As an initial screening step, we will employ mass spectrometry-based proteomics to conduct a comprehensive analysis of stem cell-derived retinal pigment epithelium (RPE) cells from CHM patients. Subsequently, we will validate the most relevant targets using our mouse model of CHM. 

Our research has the potential to uncover novel therapeutic targets for CHM, paving the way for innovative treatments that could significantly improve the quality of life of those affected by this condition.  



Period: 2022 - Ongoing

Funding: