• Dr. Robert Fox, a neurologist, discussed current research into progressive forms of multiple sclerosis (MS) at 2021 Consortium of Multiple Sclerosis Centers Annual Meeting.
• Researchers are reassessing how they classify different types of MS as they discover people can show signs and symptoms of both relapsing and progressive MS.
• Dozens of potential treatments and therapies are under development for progressive MS as researchers analyze cell behavior, hormones, and immune-system metabolism.

Researchers are taking a fresh look at new treatments and therapies that address progressive forms of multiple sclerosis. According to Dr. Robert Fox, who opened this year’s Consortium of Multiple Sclerosis Centers Annual Meeting, promising treatments involving stem cell transplants, metabolic support, and cellular interplay could be on the horizon.

Dr. Fox is a neurologist at the Mellen Center for Multiple Sclerosis and vice chair for research at the Neurological Institute with Cleveland Clinic. During his presentation at the event in October, Dr. Fox reviewed the latest findings about progressive MS and the status of new therapies.

Scientists Review Traditional MS Classifications

Historically, the majority of people living with relapsing-remitting MS (RRMS) have eventually transitioned to a more progressive form of the condition. Past studies have found that half of those diagnosed with RRMS would transition to secondary progressive MS (SPMS) within 10 years, and 90 percent would transition within 25 years. According to My-MS.org, recently developed disease-modifying therapies (DMTs) “seem to have an impact on disease progression, but they are still unable to halt the progression completely. It’s still too soon, however, to see the specific extent to which the DMTs have changed or more importantly delayed the transition to SPMS.”

Scientists have found it challenging to develop treatments that are effective for progressive MS. Now, some researchers are looking at the disease anew to better understand what it means to have progressive MS, Dr. Fox told MyMSTeam.

“We used to think you either have the relapsing stage of MS or the progressive stage,” he noted. “But what we’ve come to realize is that they occur at the same time. We’re starting to deemphasize ‘Do you have relapsing-remitting MS or secondary progressive MS?’ and instead we’re asking two parallel questions: Is there active inflammation? And is there ongoing progression?”

The traditional classifications are not being abandoned, but clinicians are recognizing that these two different aspects of MS — active inflammation and progression — can occur together. The evolving view is that stages of disease are not sequential but are actually overlapping or parallel.

Diagnosing SPMS continues to be challenging. Studies have indicated that it may take two to three years longer to diagnose primary progressive MS than it takes to diagnose RRMS. While magnetic resonance imaging (MRI) may show areas of abnormality that suggest MS, it can’t be used to make a definitive diagnosis.

“The problem is there are no definitive imaging features that differentiate between primary progressive and secondary progressive MS, and there are no definitive imaging features that differentiate progressive MS from relapsing,” Dr. Fox said.

Beyond imaging, doctors look to the behavior of cells that may lead to the neurodegeneration that causes progressive MS. Relapsing MS involves a malfunction of the peripheral immune system (a collective term to describe the immune responses that occur outside the brain) whereby the white blood cells leave the bloodstream, go into the brain, and attack it.

“What we’ve come to find is that progressive MS is probably not an extension of RRMS — instead, there’s probably something within the brain that is driving progressive MS,” Dr. Fox said. “So if it’s being driven by something within the brain, we’re looking at those cells that live within the brain.”

Cells, Treatments Are Under Review

Cells of interest are astrocytes, microglia, and oligodendrocytes. Oligodendrocytes are the cells that extend their arms to put the myelin sheath (an insulating layer) around the axon (nerve fiber). Astrocytes are specialized support cells within the brain, which are thought to be influenced by environmental challenges, including dietary factors. Microglia are the “trash collectors” that remove debris or pathogens from the brain.

“There are many different potential pathways of interaction of the astrocytes with these other cells that could be driving the pathway forward of progressive MS,” said Dr. Fox. Scientists are still working to figure out how these cells may interact to promote progressive MS.

Researchers are developing medications that take these cells into consideration and try to alter what they do. Other therapies are looking at metabolic support, to try to support the metabolism of the immune system. Another possible treatment involves evaluating how estriol (an estrogen hormone) impacts both the immune system and remyelination (to create new myelin sheaths).

In all, Fox offered a list of 27 agents that are currently under development for progressive MS, along with approved relapsing MS therapies indicated for active secondary progressive disease. Although many of the therapies are in later-stage trials, their effectiveness is still inconclusive at this time.

“I wish I could handicap which therapies look more promising and have greater potential,” said Dr. Fox. “But at this point, we don’t really know, so we have to wait until the trials are done.”

Not all potential treatments pan out as investigators hope. Dr. Fox pointed to biotin, for which researchers had great expectations. “We were excited about high-dose biotin, but unfortunately, that large trial finished about a year ago and was indeed negative,” said Fox.

Researchers are also investigating stem cell treatments. Stem cell research is of particular interest in progressive MS because of its potential to promote remyelination and repair. One approach is to replace stem cells in order to stimulate the brain’s repair system, while another path is to use drugs to stimulate stem cells within the brain in the spinal cord of an individual.

These new developments signal a fresh approach to treating progressive MS, Dr. Fox told MyMSTeam. “There is renewed focus and there is renewed energy around progressive MS,” he said. “Although we have been all excited about treatments for relapsing MS and we continue to be excited about that, we’re also moving on and addressing the huge unmet need of progressive MS.”