Researchers at the Toronto-based Center for Addiction and Mental Health (CAMH) say they have discovered a promising new approach to treat multiple sclerosis (MS). In a new study, they've identified a previously unknown change in the spinal cord related to MS, and a way to alter this change to reduce the nerve cell damage that occurs with the disease.
This research, which could lead to the development of new types of drugs to treat MS, was led by Fang Liu, Ph.D., senior scientist in CAMH's Campbell Family Mental Health Research Institute and professor in the department of psychiatry, University of Toronto.
The study (“Blocking the GluR2-GAPDH Interaction Ameliorates Experimental Autoimmune Encephalomyelitis”) appears in the Annals of Clinical and Translational Neurology.
Multiple sclerosis (MS) is a progressive, often disabling neurological disease, which is most often diagnosed among young adults between the ages of 15 and 40. “We've identified a new biological target for MS therapy,” says Dr. Liu. This approach aims to stop the nerve damage related to glutamate, an important neurotransmitter.
The focus of her team's investigation was a spinal cord change that involved a protein, which attaches to a specific cell receptor for the glutamate neurotransmitter. This linked receptor-protein complex was present at higher levels in spinal cord tissues of deceased MS patients and in animal models for MS.
The potential for a new MS treatment is based on what Dr. Liu's team was able to show after this discovery. Using techniques developed in her lab, the researchers created a new peptide to try and disrupt this change in animal models of MS.
“We…developed a peptide that can specifically disrupt the GluR2-GAPDH complex,” wrote the investigators. “This peptide greatly improves neurological function in EAE [experimental autoimmune encephalitis] mice. This peptide also reduces neuron death, rescues demyelination, increases oligodendrocyte survival and reduces axonal damage in the spinal cord in EAE mice. More importantly, this peptide has no direct suppressive effect on naïve T-cell responses or basal neurotransmission.”
“We found that our peptide disrupted this linkage, and led to major improvements in neurological functioning,” says Dr. Liu. Specifically, motor function was significantly better compared to a comparison group.
In MS, inflammation damages myelin in the central nervous system (CNS), which can harm the underlying nerves and interrupt the transmission of nerve impulses. MS is associated with a wide variety of symptoms, based on where the damage occurs in the CNS.
Importantly, the new peptide didn't appear to suppress the body's immune response system directly, and did not impair physiologically essential neuron transmission in the brain, a common side effect for drugs targeting the glutamate system, notes Dr. Liu.
“Our priority now would be to extend this research and determine how this discovery can be translated into treatment for patients,” she says.