Scientists may have found a promising lead to follow for treating multiple sclerosis (MS) — the most widespread neurological disorder disabling young adults between the ages of 20 and 40.
Individuals with MS can suffer from almost any nervous system-related functional decline with varying intensities. Defects in vision, sensation, balance, and coordination are the most common symptoms.
Recent evidence suggests that, in the case of MS, glutamate — a brain chemical that relays signals between nerve cells — excessively stimulates nerve cells, causing them to be damaged or, at times, killed. Glutamate mediates its effects on nerve cells by binding to and activating an AMPA receptor, which is a protein located on the surface of nerve cells.
Dr. Fang Liu and her team from the Centre for Addiction and Mental Health and the Department of Psychiatry at the University of Toronto were looking for a plan of attack to block specific AMPA receptors that get excessively activated by glutamate. “This is an important distinction from normal AMPA receptors that otherwise play a critical role in learning and memory,” explains Dr. Dongxu Zhai, the lead researcher of the project.
Published in Annals of Clinical and Translational Neurology early this year, the team detailed how it tracked down those specific AMPA receptors, suggesting a novel therapeutic target for the development of MS medications.
The researchers referred to one of their previous studies showing how excessively activated AMPA receptors by glutamate can initiate cell death through a protein-protein two-some between a part of AMPA receptor and another enzyme, which is also a protein.
In the current study, they showed that the same complex was present at significantly higher levels in dead tissue from MS patients and mice that mimic MS symptoms.
The team then wondered whether breaking up this protein-pair would reduce nerve cell death in the sick mice. To this end, Zhai designed a peptide — a small chemical chain — for subsequent treatment.
The sick mice treated with the peptide showed regrowth of nerve cells, increased survival of parent cells from which the insulating coat around the nerve cells grow, and the rescue of thinning of the very same coat.
Commenting on the putative drug-like features of the peptide, Zhai adds, “Based on our current experiment, the treatment of this peptide had very minimum side effects and that is very encouraging.” The team did not detect any direct effect of the peptide on the immune system of the mice model.
“Hopefully we can develop a drug based on this peptide. Some challenges, however, exist — one of which is we now need to determine the best route of administration since that can greatly affect the efficacy of the drug,” Zhai remarks.