Project description
Gene therapy targets Charcot-Marie-Tooth disease
Charcot-Marie-Tooth (CMT) disease encompasses a group of inherited nerve disorders affecting motor and sensory neurons primarily in the feet, legs, hands, and arms. Typically identified in adolescence, progression continues throughout the patient’s life. There is no effective pharmacological treatment for CMT. Building on their groundbreaking work identifying the molecular mechanism underlying CMT caused by mutations in the gene coding glycyl-tRNA synthetase, the ERC-funded tRNAHigh project aims to advance a gene therapy to elevate glycyl-tRNA expression levels. The team plans to identify the optimal viral vector for vector-mediated gene transfer, and the optimal administration route and dose. The project also plans to secure personnel and funding for its spin-out company and obtain a patent for the optimal gene therapy vector.
Objective
Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disease,
characterized by selective degeneration of peripheral motor and sensory neurons, leading to
progressive muscle weakness and wasting, and sensory dysfunction. Currently, no effective,
FDA/EMA-approved therapies are available for CMT, necessitating life-long symptomatic treatment.
We recently identified the molecular mechanism underlying CMT caused by mutations in glycyl-tRNA
synthetase (GlyRS). We showed that transgenic overexpression of the glycyl-transfer RNA (tRNA-Gly)
fully rescues peripheral neuropathy in two CMT-GlyRS mouse models. Furthermore, we present
preliminary data showing that viral vector-mediated gene transfer of tRNA-Gly administered to newborn,
presymptomatic CMT-GlyRS mice fully rescues their peripheral neuropathy phenotypes.
In this project we will optimize tRNA-Gly gene therapy, including identification of the optimal viral vector,
administration route, and dose to target adult motor and sensory neurons. Next to that, the project will
focus on the development of a business roadmap for XtRNA Bio, the spin-out company that I recently
co- founded with NLC Health Ventures. XtRNA Bio intends to raise significant pre-seed funding and
recruit presonnel, including an experienced CEO who will secure additional funds for continued
preclinical and clinical development of tRNA-Gly gene therapy. Finally, once identified, we will patent
the optimal gene therapy construct.
In all, this proposal constitutes a crucial step towards a first effective therapy for CMT-GlyRS and CMT
in general.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine neurology
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-POC
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
6525 XZ Nijmegen
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.