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Novel drugs for the treatment of multiple sclerosis

Two major awards have been received to fund the development of a neuroprotective therapy to prevent nervous system damage and progression in MS.

Congratulations to Dr Iain Greig on the award of over $1.5 million in funding to support the development of first-in-class drugs for the treatment of multiple sclerosis. The Kosterlitz team are providing the synthetic and medicinal chemistry expertise for an exciting new partnership with the Centre for Addiction and Mental Health (CAMH) in Toronto.

In a major boost for multiple sclerosis (MS), a promising new treatment that may prevent nervous system damage in MS will be developed. The research will be led by Dr Fang Liu of CAMH, working with Dr Iain Greig and the Kosterlitz Centre for Therapeutics, with support from major new grants funded by the Canadian Institutes of Health Research (CIHR), the National MS Society and the MS Society of Canada. 

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. In progressive forms of MS, chronic neurodegeneration occurs that results in the steady accumulation of disability. Thus far, therapies that are effective for relapsing MS have shown limited to no efficacy in progressive MS. Canada and Scotland have some of the highest rates of MS in the world.

In earlier MS research, also funded by the National MS Society and the MS Society of Canada, Dr Liu had previously showed that blocking the interaction between two proteins that form a complex -- GluR2 and GAPDH -- provides neuroprotection by preventing nerve tissue damage caused by too much of the neurotransmitter glutamate, which is known as excitotoxicity. These results were published in the Annals of Clinical and Translational Neurology in 2015. Many attempts to prevent excitotoxicity in the past have impaired normal communications between neurons in the brain.

To create an effective, long-lasting medication for treatment, Dr. Liu’s team formed a collaboration with Dr. Iain Greig, a Visiting Professor from the University of Toronto’s CCDR. Dr. Greig’s team at the University of Aberdeen developed small molecules capable of blocking the GluR2-GAPDH complex. Small molecules are common in drug development as they can be taken orally and are easily absorbed by the body.

The team has identified two chemically distinct early lead compounds that reduce excitotoxicity. They are now seeking to make new molecules with optimal properties for drug development and to test the most promising in MS models.

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