- 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 support myelin regeneration and has the potential to stop and even cure the damage caused by MS.
Multiple sclerosis (MS) is an autoimmune disease in which the immune system
When immune cells attack the myelin sheath, it causes inflammation and interrupts the transmission of nerve impulses throughout the body. This can lead to neurological symptoms, including:
- Muscle weakness
- Numbness, tingling and pain
- Bowel and bladder problems
- fatigue
- Dizziness and vertigo
- Mobility problems
- Loss of vision.
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 the myelin around nerve cells and thus potentially reverse the damage caused by MS.
The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).
“Current treatments for MS work by attacking the immune system, making it less likely to attack the protective myelin sheath around nerves. But we also need to find ways to repair the damage to myelin that has already occurred.”
— Caitlin Astbury, research communications manager at the MS Society, who was not involved in the study.
The myelin sheath that surrounds and protects nerve cells is made up of cells called oligodendrocytes. In a person with MS, these cells are lost, so damaged myelin sheaths cannot be repaired.
In this latest study, researchers used a toxin from green mamba venom to identify and localize a receptor protein, M1R, on oligodendrocyte precursor cells (OPCs), which do not differentiate into oligodendrocytes in people with MS.
The newly developed drug PIPE-307 blocks the M1R receptor and thus enables the differentiation of OPCs into oligodendrocytes, which can then form new myelin sheaths.
After identifying the receptor and showing that the drug could block it, the researchers tested the effectiveness in vitro in isolated OPCs.
The drug blocked the M1R receptor better than existing drugs, causing the OPCs to mature into oligodendrocytes and begin to myelinate nearby nerve axons. It was also able to cross the blood-brain barrier, potentially treating damaged nerve cells in the brain.
Jonah Chan, PhD, Debbie and Andy Rachleff Distinguished Professor of Neurology at UCSF and senior author of the paper, said in a press release:
“Ten years ago, we discovered a way for the body to regenerate its myelin in response to the right molecular signal, thereby reversing the effects of MS.”
“By carefully studying the biology of remyelination, we have developed a precise therapy to activate it – the first of a new class of MS therapies,” he added.
The researchers then conducted further in vitro Studies using mouse brain tissue slices found that PIPE-307 increased myelination of nerve cell axons.
The next step was to administer the drug orally to genetically modified mice that developed inflammatory demyelination as a model for MS (MOG-EAE mice). The mice not only showed increased myelination of nerve cells, but also regained some lost functions.
In a Phase 1 study in healthy people, PIPE-307 was well tolerated and had no adverse effects, so researchers are now moving on to a Phase 2 trial to assess whether it is an effective treatment for people with MS.
Astbury urged caution regarding the results and said 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 truly understand whether this drug works, we need to wait for the results of clinical trials in MS patients.”
Other drugs such as clemastine, a first-generation antihistamine, have been studied for their potential effectiveness in myelin repair with varying degrees of success.
Ari Green, MD, chief of the Division of Neuroimmunology and Glial Biology in the Department of Neurology at UCSF and co-author of the article, commented in the press release:
“Clemastine is not a targeted drug that affects several different pathways in the body,” he said. “But from the beginning, we saw that its pharmacology involving muscarinic receptors could point us toward the next generation of restorative therapies in MS.”
And their results suggest that PIPE-307 is more effective at blocking the M1R receptor and restoring myelin.
However, it is still a very early stage, and the Phase 2 study that is just beginning must show that the drug is not only effective, but also safe to use and has no significant side effects.
There is a huge need for effective treatments for people with MS, Astbury concluded:
“There are more than 150,000 people living with MS in the UK and many do not have access to treatment. In the future, we would 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, PIPE-307 could potentially be part of this combination.
