Hope for Progressive MS Therapies Depends on New Lesion Map
Last updated: November 2021
If you have progressive multiple sclerosis, either primary (PPMS) or secondary (SPMS), you may be interested in hearing about this hopeful new effort by scientists to repair ongoing MS damage caused by chronic inflammation.
Taking a look at smoldering plaques
The chief problem with MS rests in the ongoing damage of nerve fibers, demyelination, caused by attacks from the immune system. These attacks can lead to the problem of chronic inflammation.
For people with relapsing-remitting forms of MS, the attacks can come and go, leaving relatively quiet periods between them. Sometimes, the brain may even be able to remyelinate or repair some of this damage, if given enough time and space to do so.1
But for people with progressive MS, lesion activity is ongoing and chronic, leaving behind damage sometimes referred to as smoldering plaques.2This perpetual inflammatory state is considered by some to be the hallmark of the more aggressive and disabling form of MS.3
Researchers at the National Institutes of Health have been working to capture this blueprint of smoldering plaques at the cellular level.4 Their goal? To identify genes within cells that might be useful for assisting the brain with lesion repair. They also want to find new therapeutic targets for treating people with progressive MS.
A map with new directions
Very recently, a study published in Nature reported that scientists have finally been able to create this comprehensive blueprint. The map was built using a technology known as single-cell RNA sequencing to catalog the genetic patterns in cells that are affected by lesion activity.5
Overall, more than 66,000 cells and their genetic behaviors have been identified and analyzed as part of this comprehensive lesion map.
Thanks to information gleaned from this new map, scientists have been able to spot a specific set of cells in people with progressive MS which may ultimately be responsible for driving the chronic inflammation that is so problematic in progressive forms of MS.
The new map helps scientists to look more closely at the biggest troublemaker involved: the microglia. Chronic active MS lesions are characterized by a slowly expanding perimeter of immune system cells known as microglia.
Tracking one likely culprit
Microglia are normally tasked to protect brain tissues, but in MS they can become overactive. When this happens, they leave behind toxic substances that cause damage to nerve cells. Along with these microglia, astrocytes and lymphocytes are two other kinds of brain cells which might also contribute to damage in people with MS.
The newly detailed blueprint shows that, while astrocytes and lymphocytes, cells that are part of the immune system, do contribute to progressive demyelination, microglia is still the chief villain, found in the greatest abundance around the edges of lesions.
In particular, a gene is known as C1q, an ancient protein of the immune system, has been singled out as being a chief driver of inflammation within clusters of microglia. It’s now being considered the likely culprit in progressive disease forms.
This is great news. Being able to see cell behaviors at such a detailed level gives researchers a clearer understanding of what smoldering inflammation in progressive MS looks like based on the kinds of cells that are part of these damaging networks. In the case of C1q, the scientists building this lesion map consider it possible to someday target it in a way that puts the brakes on MS progression.
This is a really important discovery
While today’s medications can be used to block new inflammation, there’s nothing to stop the inflammation already active in progressive MS.
While only about 10 percent of people with MS are diagnosed with the progressive form of the disease,6 this group of people with MS has only one medication approved by the FDA to treat their disease (ocrelizumab).7
More treatment options are urgently needed to treat those most disabled by this neurological disease. The new lesion map provides hope that researchers are now more enabled than ever to achieve this important therapy milestone.
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