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.
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 has one of the highest rates of MS in the world, according to the Atlas of MS.
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 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.
This research also benefited from past proof-of-principle funding awards from CAMH’s Campbell Family Mental Health Research Institute and the Canadian Institutes of Health Research (CIHR).
The Centre for Addiction and Mental Health (CAMH) is Canada’s largest mental health and addiction teaching hospital, as well as one of the world’s leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental health and addiction issues. CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre. For more information, follow us on twitter @CAMHnews
The Centre for Collaborative Drug Research was established in 2013 and is a partnership between the University of Toronto’s Faculty of Medicine, Pharmacy and CAMH.
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The National MS Society addresses the challenges of each person affected by MS by funding cutting-edge research, driving change through advocacy, facilitating professional education, collaborating with MS organizations around the world, and providing programs and services designed to help people with MS and their families move their lives forward. The National MS Society is committed to achieving a world free of MS.
For more information, visit www.nationalMSsociety.org.
Canada has the highest rate of multiple sclerosis in the world. MS is a chronic, often disabling disease of the central nervous system comprising the brain, spinal cord and optic nerve. It is one of the most common neurological diseases affecting young adults in Canada. Most people with MS are diagnosed between the ages of 15 and 40, and the unpredictable effects of MS last for the rest of their lives. The MS Society provides services to people with MS and their families and funds research to find the cause and cure for this disease. Please visit mssociety.ca or call 1-800-268-7582 to make a donation or for more information.