Innovative strategy to treat Charcot-Marie-Tooth patients based on translational readthrough molecules by in vitro screening using CRISPR-Cas9 and iPSc technologies
Description: This project focuses on the most common inherited peripheral neuropathy in humans: Charcot-Marie-Tooth disease (CMT). More than 90 altered genes may be responsible for CMT. Around 10% of the CMT mutations are Premature STOP Codon (PTC). Our main objective is to develop effective therapeutic approaches to treat CMT patients harboring PTC mutations, thanks to the work of three complementary teams. The Limoges coordinator team managed the creation of human induced pluripotent stem cells (iPSc) and their differentiation into motoneurons (affected cells in CMT patients), providing then an excellent in vitro model to test drugs. The Bordeaux team is an expert in CRISPR-Cas9 technology and will be able to generate PTC mutations in CMT genes on Limoges’ iPSc. We will then investigate if the new readthrough molecules, identified by Lille team, are efficient on these generated motoneurons. This project could also be the proof of concept to treat other inherited diseases due to PTC mutations.
Funder: Agence Nationale de la Recherche
Amount: €413,800
Funding type: research
Funder scheme: AAPG2020
Start date: 2021-01-01
Investigator: Anne-Sophie LIA (lead)
Institution: Maintenance Myélinique et Neuropathies Périphériques
Funded outputs count: 6
Funder award ID: ANR-20-CE17-0026
OpenAlex ID: G5435534945