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Identification of novel therapeutic targets for primary and secondary progressive multiple sclerosis

Progression of disability and the inability to participate in usual activities often occurs in patients suffering from Multiple Sclerosis (MS). In secondary-progressive MS, which follows earlier relapsing-remitting disease, neurodegeneration proceeds gradually unaffected by currently available treatments, which is a major cause of disability.  Currently, there is no treatment for this type of MS. As a misguided or malfunctioning immune system is at work in MS, we reasoned that substances released from certain activated immune system cells known as lymphocytes may be toxic to neurons.  We discovered that a molecule called granzyme was released from these lymphocytes, and granzyme can cause injury to neurons and brain stem cells. This damage would prevent any attempts of the brain to regenerate.

We also discovered that granzyme causes an increased expression of a type of potassium channel on the surface of the nerve cells and brain stem cells. If it were to be blocked, one could not only prevent the effects of granzyme but also promote regeneration.

This potassium channel thus represents a novel target for drug development.  These findings are in various stages of publication.  This research is conducted by members of the Neuorvirology and Neuroimmunology Laboratory.

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