How drugs could repair damage from multiple sclerosis

How drugs could repair damage from multiple sclerosis

NIH August 14, 2018

At a Glance

  • Drugs that help repair the nerve cell lining that’s damaged in multiple sclerosis were found to target certain enzymes.
  • The finding could help researchers develop new treatments for multiple sclerosis.
The team used a series of laboratory techniques to examine how drugs interact with the molecules in the body that are involved in myelin production. They found that miconazole and eight other related drugs all blocked an enzyme called CYP51. Blocking CYP51 encouraged stem cells to form new oligodendrocytes. These are the cells that create the myelin coatings around nerve cells.

CYP51 is part of the molecular pathway that produces cholesterol. The researchers discovered that blocking two other enzymes in that pathway also promoted oligodendrocyte production.
The boost in oligodendrocyte production appeared to be due to buildup of a specific type of cholesterol precursor (called 8,9-unsaturated sterols) when any of the three enzymes was blocked. When the researchers treated stem cells with 8,9-unsaturated sterols, they saw oligodendrocyte production rise.

The team next screened over 3,000 approved drugs and other small molecules for their ability to promote oligodendrocyte production. The top ten all caused a buildup of 8,9-unsaturated sterols.
When tested on human stem cells grown in the laboratory, drugs or genetic manipulations that targeted any one of the three enzymes caused oligodendrocytes to form and start laying down myelin. In mice with damage to myelin in their spinal cords, injection of drugs that targeted one of the enzymes caused restoration of myelin in the damaged tissue.
“We were shocked to find that almost all of these previously identified molecules share the ability to inhibit specific enzymes that help to make cholesterol. This insight reorients drug discovery efforts onto these novel, druggable targets,” Adams says.
The researchers have formed a company to build on these findings and develop therapeutics to promote myelin repair.


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