Researchers have developed a new therapy that can restore the myelination process in animal models of multiple sclerosis.
- Multiple sclerosis (MS) is a so-called demyelinating disease. It causes a breakdown of the protective insulation that surrounds nerve cells, called the myelin sheath.
- Researchers have identified a receptor whose inhibition effectively restores the remyelination process and, from there, have developed a new drug to activate it.
- PIPE-307 therapy, which demonstrated safety in a Phase I clinical trial in 2021, is currently being tested in MS patients in Phase II.
Multiple sclerosis (MS) is a so-called demyelinating disease. It causes the protective insulation that surrounds nerve cells, called the myelin sheath, to break down, leaving their axons (which transmit signals in the form of electrical impulses) exposed like bare wires. This causes problems with motor and sensory functioning, balance and vision, and if left untreated, leads to paralysis and a shortened life expectancy.
Myelin destruction is driven by both an excessive inflammatory response and an inability to restore this sheath. By limiting inflammation and myelin loss, current treatments “only” slow the progression of MS. However, a team of researchers has just developed a new drug that could change the game by regenerating myelin and reversing the damage caused by the disease.
Restoring the remyelination process in MS patients
Scientists from the University of California, San Francisco (UCSF) and Contineum Therapeutics in the United States have identified a receptor whose inhibition allows the remyelination process to be effectively restored and, from there, have “developed a therapy to activate it – the first in a new class of MS therapies”according to a press release.
Oligodendrocytes, the cells that produce myelin, are gradually lost in MS patients. But the new therapy, called PIPE-307 and based on the drug clemastine that has already been shown to be effective against the disease, targets a specific receptor (M1R) on certain dormant brain cells and, in doing so, prompts them to mature into oligodendrocytes. Indeed, once the receptor is blocked, the oligodendrocytes can spring into action, wrapping themselves around axons to form a new myelin sheath.
Surprisingly, it was thanks to a toxin found in the deadly venom of the green mamba snake, called MT7, that the researchers were able to determine exactly where the M1R receptor was located in the brain. “MT7, which is delightfully selective for M1R, fits the bill”they specify. This made it possible to confirm that “M1R was the right target for a remyelinating drug,” Then “to make a drug that blocked it exclusively.”
A therapy currently being tested on MS patients
The researchers, whose work was published in the journal PNASthen tested the effects of the new treatment in the laboratory and in animal models of MS using a series of tools to monitor remyelination. As a result, “PIPE-307 blocked the M1R receptor much better than clemastine; it prompted cells to mature into oligodendrocytes and begin myelinated neighboring axons; and it crossed the blood-brain barrier.” In other words, it was a success.
PIPE-307 therapy, which demonstrated its safety with a phase I clinical trial in 2021, is currently being tested in MS patients in phase II. If validated, “We might have a chance not only to stop their disease, but to cure it.”the authors conclude.
