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 the Centre for Addiction and Mental Health (CAMH), working with University of Toronto’s Centre for Collaborative Drug Research (CCDR), with support from a major new grant funded by the National MS Society and the MS Society of Canada.

“We will build upon our earlier discovery of a new MS treatment approach, to develop new molecules with optimal properties for drug development,” says Dr. Fang Liu, Senior Scientist in CAMH’s Campbell Family Mental Health Research Institute and Professor in the Department of Psychiatry at the University of Toronto.

CAMH is developing a neuroprotective therapy to prevent nervous system damage and progression in MS. Dr. Liu and her team have expertise in developing peptide molecules that, in the lab, disrupt abnormal activity on specific neurons, to reduce symptoms of illness with minimal side effects. They have successfully applied this approach to create potential new treatments for depression, schizophrenia and other brain–based illnesses.

In earlier MS research, also funded by the National MS Society and the MS Society of Canada, the team 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 journal 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 medicinal chemistry expert 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. “The National MS Society is committed to accelerating development of commercial research opportunities towards clinical use,” said Mark Allegretta, PhD, Associate Vice President of Commercial Research at the Society. “We are pleased to partner with the MS Society of Canada to support this medicinal chemistry effort to improve the properties of small molecules targeting the GluR2 – GAPDH complex.”

The initiative is a multi–institution effort. “This is exactly the type of exciting drug discovery partnership opportunity that the Centre for Collaborative Drug Research seeks to enable,” says Prof. Ruth Ross, Director of the Centre. The CCDR was established in 2013 and is a partnership between the University of Toronto’s Faculty of Medicine, Pharmacy and CAMH.