At Race to Erase MS 2023, scientists gathered to discuss the latest research, from ‘designer estrogen’ aimed at preventing brain atrophy in women to next-gen blood tests powered by AI.

By Becky Upham

June 7, 2023FacebookTwitterPinterestCopy Link

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In 1993, interferon beta-1b made history as the first drug to ever be approved for multiple sclerosis (MS). It also happens to be the year that Nancy Davis founded Race to Erase MS, an organization dedicated to funding cutting-edge, aggressive, and promising research in pursuit of a cure. To date, the organization has raised over $50 million for multiple sclerosis research.

On June 3, 2023, the organization gathered top MS researchers from around the United States for its MS Forum and Expo in Los Angeles, to discuss the latest advances in treatments. Here are some highlights from the event.

DMTs Have Transformed MS Treatment but There Is Still Much Work to Be Done

Emmanuelle Waubant, MD, PhD, a professor of neurology and MS researcher at University of California in San Francisco, began her presentation on MS disease-modifying therapies (DMTs) by highlighting the “remarkable transformation” of the treatment landscape, with more than 25 medications now available to treat disease progression.

There are different classes or families of DMTs, some of which have several options within them, whereas other classes may have limited options, noted Dr. Waubant. “There’s a lot of companies working to improve the tolerability, for example, of these medications and put new agents on the market in these families,” she said.

Doctors currently prescribe DMTs to prevent flares, halt new scars on MRI scans, and slow or stave off disability progression, said Waubant.

“However, the challenge lies in finding drugs that can actually prevent disability once it starts progressing insidiously. That’s a really huge field of research right now,” she said.

Potential MS Treatments on the Horizon

BTK Inhibitors

These drugs, which fight inflammation in a unique way compared with existing medications, are currently among the most promising candidates under development. Their fate regarding U.S. Food and Drug Administration approval will be determined once clinical trials conclude. BTK inhibitors are being tested in both relapsing and progressive MS to determine their effectiveness.

CD40 Ligand Inhibitors

This drug class is designed to combat inflammation in both relapsing and progressive MS. The aim is to prevent inflammation and its associated effects.

This supplement is an amino acid that Waubant is studying for people with progressive MS in a trial funded by the U.S. Department of Defense.

MS Drugs With New Targets

Researchers are exploring medications or treatments that specifically target the Epstein-Barr virus (EBV), with at least one trial already underway.

Nasal Spray for MS

Howard Weiner, MD, a professor of neurology at Harvard Medical School and director of the Partners Multiple Sclerosis Center at the Brigham and Women’s Hospital in Boston, discussed his ongoing research to develop an MS nasal spray.

“It’s a monoclonal antibody that we spray in the nose, and we found that it helps in animal models of progressive MS — they don’t progress as much,” he said.

Over the last couple of years, the nasal spray has been studied in six MS patients. So far, it’s been well tolerated, said Dr. Weiner. “Some of them were feeling better, and we saw changes in the brain, PET scanning.”

Because of these successes, double-blind trials are in the works, he added.

Drugs in Development to Promote Myelin Repair

In MS, myelin becomes damaged, leading to MS progression and accumulation of disability — which could be a clue to finding better treatment.

For instance, how is it that some people with MS who are mostly confined to a wheelchair have days where they can get up and walk across their kitchen? That question was posed by Peter Calabresi, MD, the director of the division of neuroimmunology and a professor of neurology at Johns Hopkins Medicine in Baltimore.

“That doesn’t happen in spinal cord injury. So there are the nerves [in MS] that are probably still intact enough to conduct the impulses in there. … The goal of my research right now is to figure out how to make that happen for everyone in a more consistent manner, rather than just once,” said Dr. Calabresi.

There is evidence of myelin repair in the tissues of some people who do very well while living with MS, and new research is looking at how drugs could facilitate this, he said.

Finding New Targets in the Brain to Promote Myelin Repair

Current MS drugs mostly target the kind of inflammation that circulates in immune cells in the blood that come to your spleen and lymph nodes, Calabresi explained.

“Now we recognize that there’s a different kind of inflammation in the brain, in some of the brain cells themselves, called glial cells. We thought they were ‘glue’ cells that just held the nerves together, but they actually can act as kind of an immune cell,” he said.

These cells are part of the “forest fire” of MS relapses, said Calabresi. Current MS medications act as “helicopters that come in and dump monoclonal antibodies on to put out that fire, but it doesn’t put out the smoldering embers and inflammation” that still exists in the glial cells.

Calabresi believes that identifying new targets on astrocytes and microglia, specific types of glial cells, could hold the key to myelin repair. “The good news is that there are some amazing technologies that allow us to identify these targets,” he said.

One example is a technology called single cell RNAseq, that allows scientists to “look inside” every cell to see if they are still functioning properly or doing damage, he said.

Many new targets have been identified in the last 20 years, said Calabresi. “We’re now developing drugs that get into the brain that will test these hypotheses, and something’s bound to work. I really think we’re just on the precipice of getting something that will repair the damage,” he said.

Targeting Midlife Brain Atrophy and Changes in MS

Previously, it was thought that the transition from relapsing-remitting to secondary-progressive MS was primarily influenced by disease duration, said Rhonda Voskuhl, MD, a professor of neurology and director of the MS program at UCLA Health, in her talk on MS and aging.

“Further analysis of that data by many groups showed that it’s actually not so much disease duration that leads to this transition to this progressive disability phase — it’s aging,” she said. Specifically, the time when a person is in their fifties is bad for MS, said Dr. Voskuhl.

This change is due to “immune senescence,” the gradual decline of immune system function that comes with age. “Older people are more likely to get infections and cancers. But what happens to the brain? The brain has neurodegeneration, and even during health, there’s brain atrophy — people have cognitive decline,” she said. Given that, it makes sense that a person with MS who has neurodegenerative aspects of their disease will get worse with aging, said Voskuhl.

She pointed out that transitioning from relapsing-remitting to secondary-progressive MS is not accompanied by a sudden increase in enhancing lesions or relapses. Instead, these patients experience fewer relapses but show an increase in disability primarily associated with brain atrophy, particularly in areas affected by aging, she said.

There are potential avenues for intervention, including examining the role of hormones. Estrogens, known for their neuroprotective effects, and testosterone, which is converted to estrogen in the brain, are essential for optimal brain function, said Voskuhl. Menopausal women with MS have been found to experience worse disability accumulation and brain atrophy, highlighting the importance of hormone balance in MS progression.

Results so far have been promising, and Voskuhl and her team are conducting a large trial to further investigate the impact of age and sex on MS progression with a $7.2 million grant from the National Institutes of Health.

“We’re going to treat menopausal women with ‘designer estrogen,’ distinct from those typically used, to try to prevent the brain atrophy and cognitive decline that can occur with menopause,” said Voskuhl.

Blood Biomarkers in MS

New biomarkers hold promise in helping doctors and researchers understand what’s happening in the brain of someone with MS, said Weiner, in his presentation about blood biomarkers in MS.

One of the new biomarkers being developed is called NFL, he said. “Not the National Football League. This one stands for ‘neurofilament light,’ and that gets released when nerve cells are damaged. That’s something that can now be measured,” said Weiner.

“There’s another blood biomarker called GFAP, glial fibrillary acidic protein, that comes from astrocytes in the brain. And that’s more prominent in patients who are progressive, and we’re now beginning to use that in our studies,” he said.

Researchers can now use AI to look at very complex patterns, including some of the differences between relapsing disease and progressive disease, said Weiner.

For example, when people become progressive and you can’t see anything on the MRI, clinicians can find a signature in the blood to understand what’s going on, he said.

Single-cell RNA sequencing now allows investigators to analyze an enormous amount of data. “We can take, like, 10,000 cells, and in each cell, you look at 30,000 genes,” he said.

As more data on these gene patterns is gathered, eventually it can be put into a program and used for diagnosis, evaluation, and treatment, said Weiner.

What Are the Latest Trends in Multiple Sclerosis Treatment? (everydayhealth.com)