The Myelin Repair Foundation (MRF) and National Institutes of Health (NIH) will initiate a clinical trial of guanabenz in people with multiple sclerosis (MS). Guanabenz is FDA-approved for high blood pressure, but it may also prevent myelin loss. The drug could be the first for MS to protect myelin from degeneration, instead of suppressing the immune system — which is how all current MS drugs work.
MS is a chronic disease, estimated to affect 2.3 million people worldwide. The cause of MS is unknown and symptoms include loss of movement, problems with vision and sensation as well as pain. These problems are caused when myelin — the fatty substance that surrounds and insulates nerve cells — degenerates due to an autoimmune attack. When myelin is damaged, cells in the nervous system can no longer communicate effectively. MS drugs seeks to prevent the immune system from attacking myelin, but guanabenz would instead protect myelin from damage.
MRF-funded researchers reported in a Nature Communications paper that guanabenz blocks the degeneration of myelin and halts MS in animal models. Guanabenz may specifically protect oligodendrocytes from dying. The results support guanabenz as a new therapy for MS, but naturally human trials are needed.
“Guanabenz appears to enhance the cell’s own protective machinery to diminish the loss of myelin,” remarked senior study author Brian Popko, Ph.D., Jack Miller Professor of Neurological Disorders at the University of Chicago and a member of the Myelin Repair Foundation’s Research Consortium. “While there have been many efforts to stimulate remyelination, this now represents a unique protective approach. You don’t have to repair the myelin if you don’t lose it in the first place.”
“We are very pleased that guanabenz is now moving into studies in MS patients,” stated Tassie Collins, Ph.D., Vice President of Translational Medicine at the Myelin Repair Foundation. “This is a promising therapeutic approach, but it might not have been able to move forward without MRF’s participation.”
In terms of plans for the clinical trials, Phase 1 clinical studies will measure the safety and tolerability of the drug and identify an optimal dose for Phase 2 clinical studies.
Treatment outcomes for the Phase 2 trials will include measuring not just new lesions using magnetic resonance imagining (MRI), but also the status of existing lesions. This is a new measurement approach that may provide a more complete assessment of MS progression.
“Success of a trial design using this outcome measure would enable rapid and cost-effective screening of neuroprotective therapies,” noted Dr. Cortese. “This would definitively lead us into the next era of treatment strategies in MS, just as contrast-enhancing lesions did for disease-modifying immunomodulatory therapies in the 1990s.”