Until recently conventional medicine has been unable to stop the demyelination of neurons seen in MS and in some other disorders such as Guillain-Barre Syndrome or trigger the cells to repair the damaged myelin sheaths. There have been some advances in this area recently that could result in a successful drug treatment to reverse demyelination.
How drugs could repair damage from multiple sclerosis"In previous research, a team led by Dr. Paul Tesar at Case Western Reserve University and Dr. Robert Miller at George Washington University found that miconazole, an antifungal drug, activated stem cells and repaired myelin damage in mice. 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."
Asthma Drug Boosts Myelin Repair in Multiple Sclerosis Mouse Model
"A research team led by neurobiologist Professor Claire Jacob has identified an important mechanism that can be used to control the restoration of myelin sheaths following traumatic injury and in degenerative diseases. With the insights gained, the researchers were able to regenerate damaged myelin sheaths in mice by treating them with the active substance theophylline, thereby restoring their nerve cell function."
EEF1A1 deacetylation enables transcriptional activation of remyelination
Trial shows myelin repair in humans is possible
"New research presented at the MSVirtual2020 conference has shown that bexarotene, a drug developed to treat cancer, is able to repair myelin in people with relapsing MS. This is a breakthrough that scientists say is critical to their goal of stopping MS. In the trial, vision tests and some types of MRI scans showed that bexarotene could repair myelin. Participants in the trial did experience some serious side effects, including an underactive thyroid gland and high levels of fats in the blood. This means bexarotene won’t be taken forward into a Phase 3 study."
Diabetes drug metformin promotes myelin repair in rats
"Professor Robin Franklin, from the MS Society Centre for Myelin Repair, described the new findings as "one of the most significant advances in myelin repair therapies there has ever been."
"To stop MS, we need to find treatments to repair myelin. But so far we haven't been able to reach this goal. Our brains have the natural ability to regenerate myelin, the protective fatty coating around our nerves. This repair involves special myelin-making cells which are made from a type of stem cell called oligodendrocyte precursor cells (OPCs). But in MS and as we age, myelin repair stops working as well as it should.
Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells
"The age-related failure to produce oligodendrocytes from oligodendrocyte
progenitor cells (OPCs) is associated with irreversible
neurodegeneration in multiple sclerosis (MS). Consequently, regenerative
approaches have significant potential for treating chronic
demyelinating diseases. Here, we show that the differentiation potential
of adult rodent OPCs decreases with age. Aged OPCs become unresponsive
to pro-differentiation signals, suggesting intrinsic constraints on
therapeutic approaches aimed at enhancing OPC differentiation. This
decline in functional capacity is associated with hallmarks of cellular
aging, including decreased metabolic function and increased DNA damage.
Fasting or treatment with metformin can reverse these changes and
restore the regenerative capacity of aged OPCs, improving remyelination
in aged animals following focal demyelination. Aged OPCs treated with
metformin regain responsiveness to pro-differentiation signals,
suggesting synergistic effects of rejuvenation and pro-differentiation
therapies. These findings provide insight into aging-associated
remyelination failure and suggest therapeutic interventions for
reversing such declines in chronic disease."
