New compound promotes myelin healing in nervous system disorders

Scientists have developed a compound that successfully promotes the reconstruction of the protective sheath around nerve cells and is damaged in conditions such as multiple sclerosis.

In a study published today in the journal Glia, scientists have successfully described the test of the compound in mice. Researchers at Oregon Health & Science University have already begun applying the compound to a rare population of macaque monkeys at the Oregon Primate Research Center at OHSU, who are developing a disease similar to MS in the man.

"I think we'll know in about a year if this drug is exactly the right drug for human clinical trials," said lead author Larry Sherman, Ph.D., professor at OHSU of the Primate Center Neuroscience Division. "If that is not the case, we know from studies on mice that this approach can work.The question is whether this drug can be adapted to larger human brains."

The discovery culminates in more than a decade of research following a breakthrough in 2005 by Sherman's lab.

In this study, scientists discovered that a molecule called hyaluronic acid, or HA, accumulates in the brains of MS patients. In addition, scientists have linked this accumulation of HA to the failure of the maturation of cells called oligodendrocytes. Oligodendrocytes generate myelin.

Myelin, in turn, forms a protective sheath covering the axon of each nerve cell – the filiform part of a cell that transmits electrical signals between cells.

Damage to myelin is associated with MS, stroke, brain damage and some forms of dementia such as Alzheimer's disease. In addition, delayed myelination may affect infants born prematurely, resulting in brain damage or cerebral palsy.

Later studies conducted by the Sherman laboratory showed that AH is broken down into small fragments of multiple sclerosis lesions by enzymes called hyaluronidases. In collaboration with Stephen Back, MD, Ph.D., professor of pediatrics at the OHSU School of Medicine, Sherman discovered that HA fragments generated by hyaluronidases sent a signal to immature oligodendrocytes not to activate their genes myelin.

This has led researchers to explore ways to block the activity of hyaluronidase and promote remyelination.

Over the last ten years, an international team of researchers led by OHSU is committed to developing a compound that neutralizes hyaluronidase in the brains of patients with MS and other neurodegenerative diseases, restoring thus the ability of progenitor cells to transform into myelin-producing oligodendrocytes. .

The study published today describes a modified flavonoid, a class of chemicals found in fruits and vegetables, that does just that.

The compound, called S3, reverses the effect of HA in limiting the growth of oligodendrocytes and promotes functional remyelination in mice. Lead author Weiping Su, Ph.D., principal investigator at Sherman Lab, has devoted years of intensive research to discovery.

"This does not just show that myelin is coming back, but it is causing axons to shoot at a much faster rate," Sherman said. "It's exactly what you want functionally."

The next phase of the research involves testing, and possibly refining, the compound in macaque monkeys carrying a natural version of MS called Japanese macaque encephalomyelitis. This disease, which causes clinical symptoms similar to those of multiple sclerosis in humans, is the only spontaneous disease similar to MS in nonhuman primates worldwide.