Collaborative Project Will Focus on TRPM4 as Potential Therapeutic Target for MS

Collaborative Project Will Focus on TRPM4 as Potential Therapeutic Target for MS
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The German Federal Ministry of Education and Research (BMBF) has granted €1.2 million ($1.35 million) to support a project seeking to characterize the function of the protein TRPM4, a potential therapeutic target to prevent nerve cell injury associated with multiple sclerosis (MS), and to develop new drug candidates for the disease.

The project is being conducted by investigators at the University Medical Center Hamburg-Eppendorf (UKE) in collaboration with colleagues at the Fraunhofer Institute for Molecular Biology and Applied Ecology IME.

TRPM4, which stands for transient receptor potential melastatin 4, is a protein that works as a channel, opening and closing at specific times to allow ions (electrically charged small molecules) to flow in and out of cells.

Its role in the context of MS was first described by Manuel Friese, MD, head of the Institute of Neuroimmunology and Multiple Sclerosis (INIMS) at the UKE. The research revealed that in MS, TRPM4 is overly active in nerve cells due to inflammatory processes, eventually playing a role in nerve cell damage.

Therefore, it is possible that by blocking the activity of TRPM4, the extent of nerve cell damage leading up to progressive disability in MS can be reduced. This is the main rationale of the collaborative project that is now being carried out at the UKE and the Fraunhofer IME ScreeningPort.

First, investigators will focus on learning more about the molecular properties of TRPM4, their potential therapeutic target, and then assess if some of its existing drug candidates can reduce nerve cell damage in different animal models of disease.

In a prior study, the approved diabetes treatment glyburide demonstrated promising efficacy. By blocking the TRPM4 channel activity, the medicine significantly eased symptoms and preserved motor neurons in animal models of MS.

They are anticipating this approach will enable newly developed drug candidates to enter clinical testing at a later stage.

“The aim of the project is to validate TRPM4 as a suitable target structure for the newly developed drug candidates, which will be developed into the first MS therapeutics available on the market to prevent nerve cell injury,” Philip Gribbon, PhD, project coordinator from the Fraunhofer IME ScreeningPort, said in a press release.

“With this project, we want to take an academic idea to marketability of a new therapeutic agent and thus actively bridge basic research and clinical application,” Gribbon said.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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