A small molecule drug that aids in the neuroprotection of cells has been found to be effective in treating nerve damage and symptoms in mouse models of multiple sclerosis, a new study suggests. The authors said this represents a key advancement that brings this MS research closer to affecting patient care.

MS is a progressive neurological disease that currently has no cure. It is linked to a wide-range of debilitating symptoms, including problems with coordination, cognition, muscle weakness, and depression. For unknown reasons, it is more common in northern latitudes and more than twice as common in women. It is known that MS damages myelin, a protective sheath that forms around nerves in the brain and spinal cord. As the myelin damage is triggered by inflammation in the immune system, up until now all current drug treatments for MS target the immune system.

In this study, researchers at the Centre for Addiction and Mental Health treated MS in a completely different way — targeting the glutamate system. Expanding on earlier work that identified a novel drug target for the treatment of MS, CAMH researchers created a small molecule compound: ZCAN262. 

A machine learning approach was used to screen for small molecules targeting the AMPA receptor GluA2 subunit. ZCAN262 was found to prevent AMPA-mediated excitotoxicity by targeting an allosteric binding site. The molecule was found to have potent effects in restoring neurological function and myelination while reducing the immune response in MS mouse models without affecting basal neurotransmission or learning and memory. 

Results of animal model studies sometimes do not translate to humans and may be years away from providing a marketable treatment. However, the researchers believe the evidence of efficacy and tolerability generated in this study ZCAN262 makes it a good candidate to be developed for human trials. The next steps in drug development will involve some further preclinical research, including investigating safety and stability of the compound.

The results have been published in the journal Science Advances.