Emerging Therapies: From the Lab to the Clinic

One of my takeaways from the 2018 ECTRIMS meeting this week is that there are thousands of researchers around the world working hard to figure out what’s going on in MS—from the very basic biology around what causes the damage to research around options for recovering functions. Some of this applied research is discussed in a blog my colleague Kathy wrote, focusing on the impacts of diet on MS.

I was especially interested in seeing how basic research around what drives brain repair mechanisms is unearthing more and more targets that present new opportunities for finding key molecules or therapies that will promote nervous system repair.

There are already a few myelin repair approaches, like clemastine and anti-LINGO, in clinical trials right now. I’m anxious to see the results, but in the meantime, I’m intrigued with what’s emerging earlier in the pipeline focusing on new targets.

For example, there’s a monoclonal antibody called elezanumab (what a mouthful). It targets “repulsive guidance molecule A,” or RGMa, a molecule that plays a role in early brain development, stopping the outgrowth of nerve endings. Some studies have suggested that RGMa is overproduced in people with MS, which could possibly reduce the amount of natural repair that would normally occur in the brain.

In animal models, elezanumab was able to promote repair of axons and myelin, and even protected against damage. Eleznumab has just been through the first phase of the 3-stage testing process that is used to determine whether a new therapy can go to market. Results of the phase 1 trial—the first time it’s been tested in people with MS—were presented this week. The trial involved people with secondary progressive MS and relapsing MS. The results suggest that it was well tolerated and didn’t cause flair-ups on MRI scans. Typically for phase 1 studies, you’re really testing primarily for safety. So the first hurtle has been jumped and I’m looking forward to seeing if this continues to show success (read the abstract).

The other side of the repair coin is the idea of “neuroprotection” —preserving and protecting the brain and spinal cord from MS damage. First results were presented from the “MS-SMART” trial, an innovative phase 2 clinical trial that compared three potential neuroprotective therapies to determine their ability to slow brain atrophy (shrinkage) in people with secondary progressive MS. A total of 445 people in the UK participated. Each of the 3 test therapies are used for other conditions, and they target different mechanisms that are thought to contribute to progressive tissue damage and MS progression.

The good news is that the results confirm that this multi-arm trial design is feasible and will speed the search for new therapies. The disappointing news is that none of the therapies showed the ability to slow down brain shrinkage. Regardless, I’m proud that the Society was one of the funders of this innovative approach to the search for solutions for people with progressive MS. 
There’s been focus on the role of immune B cells in MS ever since the success of therapies like Ocrevus (approved last year for the treatment of primary progressive MS and relapsing forms), which target these cells. I was interested to see the first reported results of a phase 2 trial of evobrutinib–an oral therapy that targets B cells, but with a different mechanism of action.
Evobrutinib inhibits an enzyme calledBruton's tyrosine kinase,” and through this mechanism, it reduces the activation of B cells and also inhibits immune cells called microglia, which have been linked to MS progression.
At this stage of the study, it’s hard to project what evobrutinib’s effects might be on progressive forms of MS, but the results showed that it was fairly well tolerated and reduced the occurrence of active brain lesions (read the abstract).

This is just a small sampling of this week’s presentations. I encourage anyone who’s interested to go to the ECTRIMS 2018 online program to explore them for yourself. 

Check out all the news from ECTRIMS 2018 on our website. 
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Mark Allegretta, PhD

Dr. Mark Allegretta is the Vice President of Research at the National MS Society, leading commercial research including partnerships developed through Fast Forward. He brings expertise in immunology and 28 years of experience in biotechnology and pharmaceutical operations to help drive the development of new therapies to stop MS and restore function.

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  • Emilia Gonzalez   Oct 13, 2018 4:11 PM
    I Will Like to be in the research
  • Thomas Pallan, M.D.   Oct 13, 2018 6:20 PM
    So where is the comment on diet?
    Tired of hearing, “just a healthy diet”

    What about Biotin??
    We know about Vit D and B12, what other supplements??
  • Tonya   Oct 15, 2018 11:42 AM
    Thankful for new research. Looks promising. Can’t wait for a cure.
  • Miriam Exelrud   Oct 23, 2018 7:23 PM
    Hello, I would like to talk in private about HERV for MS.
  • Charity Farley   Feb 12, 2019 9:50 AM
    I am a 45 year old white female. I have had MS for 23 years, hitting me at age 22 in 1996. Currently I am primary Progressive. I have had chronic pain, starting at the bottom of my skull, and travels all the way down. The bulk of my pain is in my neck and entire back.
    The pain began in my neck in February 2006. Over the years, it has gotten progressively worse. I am taking the highest amount of gabapentin and Lyrica that I can take. I have been on a slew of Narcotics, tried ketamine treatments, had blocks put in,, and have tried multiple other treatments. I also participated in an experimental MS treatment at Drexel in Philadelphia, in January 2005. This experimental treatment, being conducted by Dr Robert Schwartzman (neurology) and Dr. Brodsky (oncology), was called Hi-Dose Chemo. The purpose of the treatment was to kill off your current immune cells, using cyclophosphamide. Then, boosting your bone marrow to generate new immune cells... Which would be ignorant of the disease. My Ms appeared to be inactive for approximately 5 years, and started right back up. It was one year after receiving this treatment, is when the pain began. The only other option, in trying to at least greatly reduce the extreme pain in my neck and back, is a pain pump. I am also extremely interested in stem cell therapy.
    Thus, I would like to ask other MS patients...
    One, has anyone had a pain pump inserted, and what where were the results?
    and Two, has anyone received stem cell therapy, what were the results,, and through whom did you receive the stem cell therapy? I am extremely interested and stem cell therapy, however I am fully aware of the incredible risks in receiving stem cell therapy from unscrupulous clinics. When it comes to stem cell therapy, there's an incredible amount of companies advertising false claims that they are approved to administer stem cell Therapies, and thoughts results of these Therapies. They take advantage of the desperation of Ms patients, and other autoimmune disease patients., and illegally administer stem cell therapy that has caused extensive, permanent damage to their bodies.
    Please help! Thank you so much.