SOURCE: Xtalks

Xtalks Webinars

October 30, 2017 07:30 ET

Neuroprotective Treatment Strategies in Multiple Sclerosis, New Webinar Hosted by Xtalks

TORONTO, ON--(Marketwired - October 30, 2017) - The guest speakers for the live broadcast taking place on Friday, November 17, 2017 include Manuel Friese, MD, Professor of Neuroimmunology and Director of the Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf, and Stephen Hess, PhD, Research Leader, Ion Channels, Evotec AG.

The TRPM4 ion channel is a member of the Transient Receptor Potential Melastatin family, and is permeable to monovalent cations but impermeable to calcium. Deletion of this gene in mice ameliorates the course of disease progression in an animal model of multiple sclerosis (MS). TRPM4 deletion does not influence the disease-relevant immune response in knockout mice in the animal model of MS.

TRPM4 is expressed in murine and human neurons, and is upregulated in axons in experimental autoimmune encephalomyelitis (EAE) and MS lesions. TRPM4 deletion substantially protects neuronal cells from excitotoxic challenges and energy deficiency; in part, this is thought to be due to excessive sodium influx through activated TRPM4 channels in diseased axons. TRPM4 blockade by glibenclamide, an unspecific blocker of this channel, exerts a similar neuroprotective property as its genetic deletion.

To find a specific inhibitor of TRPM4 channels to further define their role in MS, we screened a library of 250K small drug-like molecules using cells expressing human TRPM4 channels with a membrane potential dye readout. Hits were confirmed and profiled for concentration-dependent activity at TRPM4, selectivity against TRPM5 and host HEK cells, and tested in Automated Patch Clamp assays. Selected antagonist molecules from multiple chemical series are being optimized for testing in vivo.

For more information or to register for this complimentary session, visit: Neuroprotective Treatment Strategies in Multiple Sclerosis.


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