New treatment may stop and potentially reverse some nerve damage in MS

• Multiple sclerosis (MS) is a chronic disease of the nervous system that can lead to muscle weakness, vision loss, and paralysis.
• It occurs when the immune system attacks the myelin sheath that surrounds and protects nerve cells.
• Existing treatments aim to suppress the immune system to prevent further damage to nerve cells.
• A new study has developed a treatment that can help regenerate myelin with the potential to stop and even heal the damage caused by MS.

Multiple sclerosis (MS) is an autoimmune disorder in which the immune system attacks and destroys the myelin sheath of nerve cells. It most commonly strikes people between the ages of 20 and 40. Some studies estimate that the prevalence of MS in the U.S. is close to 1 million .

When immune cells attack the myelin sheath, this causes inflammation and interrupts the passage of nerve impulses around the body, leading to neurological symptoms which may include:

• Muscle weakness
• Numbness, tingling and pain
• Bowel and bladder problems
• Fatigue
• Dizziness and vertigo
• Mobility problems
• Vision loss.

Although there is no cure, current treatments can slow the progression of the disease, reduce the number and severity of relapses, and relieve symptoms.

Now, researchers have developed a treatment that can help regenerate myelin around nerve cells, potentially reversing the damage caused by MS.

The study is published in the journal Proceedings of the National Academy of Sciences (PNAS) .

“Current treatments for MS work by targeting the immune system, making it less likely to attack the protective myelin coating around nerves. But we also need to find ways to repair the damage to myelin that has already been done.”
— Caitlin Astbury, research communications manager at the MS Society , who was not involved in the study.

Restoring the protective sheath of nerve cells

The myelin sheath that surrounds and protects nerve cells is made by cells called oligodendrocytes. In a person with MS, these cells are lost, so damaged myelin sheaths cannot be repaired.

Animal studies have shown limited success in activating oligodendrocytes and regenerating myelin. One mouse study suggests that an epigenetic approach may be effective in enhancing myelin production.

In this latest study, the researchers used a toxin from the venom of a green mamba snake to identify and locate a receptor protein, M1R, on oligodendrocyte precursor cells (OPCs), which fail to differentiate into oligodendrocytes in people with MS.

The newly developed drug — PIPE-307 — blocks the M1R receptor, allowing the OPCs to differentiate into oligodendrocytes that can then form new myelin sheaths.

Having identified the receptor and shown that the drug could block it, the researchers tested the efficacy in vitro in isolated OPCs.

The drug blocked the M1R receptor better than existing drugs, causing the OPCs to mature into oligodendrocytes and begin myelinating nerve axons nearby. It was also able to cross the blood-brain barrier so could, potentially, treat damaged nerve cells in the brain.

Jonah Chan, PhD , a Debbie and Andy Rachleff Distinguished Professor of Neurology at UCSF, senior author on the paper, said in a news release :

“Ten years ago, we discovered one way that the body can regenerate its myelin in response to the right molecular signal, winding back the consequences of MS.”

“By carefully studying the biology of remyelination, we’ve developed a precise therapy to activate it — the first of a new class of MS therapies,” he added.

Animal and phase 1 human trials show promise

The researchers then carried out further in vitro studies with slices of mouse brain tissue, finding that PIPE-307 increased the myelination of nerve cell axons.

The next step was to administer the drug orally to mice genetically modified to develop inflammatory demyelination as a model for MS (MOG-EAE mice). Not only did the mice show increased myelination of nerve cells, but they also recovered some lost function.

In a phase 1 trial in healthy people, PIPE-307 was well tolerated and had no negative effects, so the researchers are moving on to a phase 2 trial to assess whether it is an effective treatment in people with MS.

Astbury urged caution about the findings, telling Medical News Today :

“This research, which used human tissue and animals, shows that PIPE-307 has the potential to be used as a myelin repair treatment. But to really understand whether this drug will work we need to see the results from clinical trials involving people with MS.”

Early progress could give hope to MS patients

Other drugs, such as clemastine , a first-generation antihistamine , have been investigated as potential myelin repair treatments, with varying success.

Ari Green, MD , chief of the division of Neuroimmunology and Glial Biology in the UCSF Department of Neurology and co-author of the paper, commented in the news release:

“Clemastine is not a targeted drug, affecting several different pathways in the body,” he said. “But from the get-go, we saw that its pharmacology with muscarinic receptors could point us toward the next generation of restorative therapies in MS.”

And their findings suggest that PIPE-307 is more effective at blocking the M1R receptor and restoring myelin.

However, it is very early days, and the phase 2 trial that is just beginning will need to show that the drug is not only effective but also safe to use, with no significant side effects.

There is a huge need for effective treatments for people with MS, as Astbury concluded:

“More than 150,000 people live with MS in the U.K., and many don’t have access to any treatments. In the future, we’d like to see a combination of drugs that can prevent immune attacks, repair myelin, and protect nerves from further damage.”

If further trials are successful, perhaps PIPE-307 might form part of that combination.