Objective
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron degeneration that leads to progressive muscle atrophy. Currently only a few FDA-approved drugs are available for ALS, which merely extend patients life by a few months. Thus, there is an urgent need for new and more effective disease-modifying treatments. Although ALS is characterized by selective motor neuron degeneration, extensive evidence indicates that other cell types contribute to both onset and progression of ALS. An unresolved question in the ALS field is whether skeletal muscle fibers are merely bystanders or rather active contributors to motor neuron degeneration in ALS, and if so, through which biological pathways. Previous and ongoing work by the host laboratory has demonstrated the contribution of skeletal muscle in FUS-ALS, (1-2% of ALS cases). As TDP-43 cytoplasmic inclusions are a universal feature in nearly all ALS patients, assessing whether mutant TDP-43 toxicity in muscle contributes to ALS may be relevant to the broad community of ALS patients. I hypothesize that TDP-43 toxicity in skeletal muscle contributes to motor neuron degeneration and ALS-related phenotypes through specific molecular programs. I will use genetic and viral approaches to modulate mutant TDP-43 levels specifically in skeletal muscle in a TDP-43-ALS mouse model, and assess the effects on ALS-related phenotypes. Moreover, I will use single-nucleus RNA sequencing, a cutting-edge technique that became recently available, to determine for the first time the biological function of TDP-43 in skeletal muscle in the context of ALS, and to potentially identify novel therapeutic targets. Indeed, if mutant TDP-43 expression in skeletal muscle would influence the age of disease onset and/or disease progression, this would imply that therapeutic strategies for ALS should not only target motor neurons but also skeletal muscles, potentially improving ALS treatment approaches.
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.
- engineering and technology materials engineering fibers
- natural sciences biological sciences genetics RNA
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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) HORIZON-MSCA-2023-PF-01
See all projects funded under this callCoordinator
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.