The last 20 years have seen an unprecedented level of innovation in therapies to treat Multiple Sclerosis (MS) which have successfully changed the reality of what it means to be a person with MS. Multiple Sclerosis continues to be a hotbed of innovation and development for new treatment strategies which, we hope, will continue to redefine the expectations for living with Multiple Sclerosis. Currently, there remain unmet needs for therapeutic strategies, in particular, having more options for people with progressive Multiple Sclerosis as well as therapies to promote remyelination. Below, we’ve listed just a few of the therapies which are often topics of discussion in the clinic room.
Bruton’s Tyrosine Kinase Inhibitors (BTKi)
These are medications that have been used to treat certain types of cancer (as has been the case for some MS treatments in the past). They work by blocking the action of an enzyme which is involved in cell-signaling for multiple parts of the immune system. Unlike medications such as the B-cell drugs, these do not deplete cells but instead modulate their activity. Many medications for MS target a part of the immune system called the adaptive immune system, which is involved in the production of antibodies and likely plays a large role in causing MS flares. The hope for these medications is that by modulating inflammation more broadly, that they could slow relapses as well as treat progressive forms of Multiple Sclerosis, while at the same time providing an option with a lower risk of infection. One such medication, Tolebrutinib, has shown promise in trials for non-relapsing secondary progressive multiple sclerosis (nrSPMS). Another, Fenebrutinib, has shown some promise in relapsing MS.
Remyelination and Neuroprotection
This is an area of significant focus of research and development in Multiple Sclerosis, although in this case a clear promising candidate has not yet emerged. These are medications which we hope will one day help to restore the integrity of the myelin sheath (the insulating layer around nerves) which is particularly affected in conditions such as multiple sclerosis. Both remyelination and anti-inflammatory neuroprotective treatment may, especially in the first year after a flare, create conditions for the body to better heal after an episode of inflammation. These would most probably be less likely to reverse or improve symptoms which have been present for many years. Although many treatments are being investigated and are in early-phase trials, none as of yet have clearly established clinical efficacy.
Autologous Hematopoietic Stem Cell Therapies (AHSCT)
This is a type of therapy which comes with significant risk and is generally being investigated for people with highly active relapsing Multiple Sclerosis who have had ongoing flares while on the currently available highest-efficacy treatments. Although there are different types of stem cell therapies and approaches, generally these therapies work by trying to “reset” the immune system by depleting and re-infusing immune cells. As of now, further investigation, including large-scale trials, are needed to establish whether these treatments are safe and effective.
Chimeric Antigen Receptor T-cell (CAR T-cell) Therapy
CAR T-cell is a more recently emerging investigational approach which attempts to re-train one side of the body’s immune system to suppress another side. Essentially, it trains the body’s T-cells to deplete a group of cells implicated in the creation of MS flares called B-cells, which are the same cells targeted by medications such as Ocrevus, Kesimpta, and Briumvi. The goal of this therapy is to both extend the effects of treatment to cells around the brain and spinal cord which other medications may not be able to reach, and to create a lasting suppression of these cells to induce long-term remission. Early studies focused on relapsing multiple sclerosis, though studies are now ongoing in both relapsing and progressive forms of multiple sclerosis. Similar to AHSCT, this is a treatment that can come with significant short-term risks and so inclusion in trials is generally reserved for people for whom currently available treatments were ineffective.