Current Treatment Options for Multiple Sclerosis

Post by Meredith McCarty

The takeaway

MS is a degenerative disease that affects millions of people worldwide. Over the past several years numerous treatment options have emerged that can alleviate many MS symptoms and slow the progression of this disease significantly. 

What is Multiple Sclerosis (MS)?

MS is a neurological condition that affects the central nervous system (CNS), including the spinal cord and the brain. What makes this disease so complex is that individual outcomes can be unpredictable, with varying phases of disease progression and relapse among individuals. MS is commonly diagnosed in individuals experiencing cognitive problems, vision loss, numbness, or weakness, though the severity of symptoms vary greatly1. Most individuals with MS will experience periods of remission and relapse of symptoms, with different treatments that target the immune system offering therapeutic benefits. 

The hypothesized sources of the acute symptoms of MS are not only focal changes in brain pathology but also diffuse changes throughout the CNS. Focal changes include inflammation of the meninges (tissues that cover the surface of the brain and include arteries, veins, and lymphatic network), demyelination (destruction of the protective sheath surrounding neurons), and changes in the blood-brain barrier1,2. More widespread diffuse changes include neuron loss and overactivation of microglia (which support neurons in the brain)1,2. 

Current disease-modifying therapies

Most approved treatments for MS target the immune system. This is based on evidence that the acute symptoms of inflammation seen in MS are due to atypical immune system functioning. While various immune cells typically circulate through the bloodstream and target invasive or damaged cells for destruction, in MS, neuroinflammation within the CNS can lead to the accumulation of immune cells that instead attack otherwise healthy brain cells. Previously, this immune dysfunction has been thought to be caused by T-Cell action, however, treatments that target B-Cells have been found to have greater therapeutic benefit3. 

There are several disease-modifying therapies (DMTs) currently FDA-approved for MS treatment that have been shown to delay the progression of acute MS symptoms4. The mechanism of action of these DMTs is targeting B-cells for downregulation. Essentially, this is thought to slow the progression of damage to the CNS by directly targeting the immune system. These DMTs are administered either orally, intravenously (via an IV) directly and quickly, or into the hypodermis (the innermost layer of the skin), which leads to a slower absorption rate. Some research suggests different mechanisms of administration may alleviate some side effects due to the speed of the DMT reaching circulation, and the cost of treatment is also a consideration (whether it must be administered in a clinical setting4). These DMTs have been found to reduce the formation of new brain lesions, as well as MS relapse rates in many patients. They remain the most effective treatment method for MS.  

Progress in MS research

There is much current research into the underlying cause of MS, to uncover a cure for this disease. Interestingly, recent research has found that the Ebstein-Barr virus (EBV) is associated with an increased risk of developing MS. EBV is a B-Cell virus that may cause long-standing changes in B-Cells post-infection that could cause chronic inflammation in the CNS5. In healthy individuals, the number of EBV-infected cells is kept low via action by cytotoxic T-Cells that can identify these EBV-infected cells and eliminate them. If there is a deficit in the action of these cytotoxic T-Cells, this could lead EVC-infected cells to accumulate in the CNS. Indeed, a recent human study found clinical improvement in individuals with MS who were treated with cytotoxic T-Cells targeted against EBV-infected cells5.

Interestingly, research into the gut microbiome may offer clues into the cause of MS. Prior work has shown the gut microbiome (the bacteria and other microbes in the gut) plays an important role in immune regulation6. Some researchers theorize that an imbalance in the gut microbiome may lead to inflammation throughout the immune system, potentially playing a role in MS development and progression. Therapeutic strategies to regulate gut microbiome homeostasis may illuminate alternative treatments for MS. 

There is some debate as to whether a longer-lasting increase in chronic inflammation may be the cause of progressive MS symptoms over time, while more acute symptoms may be caused by focal infiltration of the CNS leading to acute inflammatory damage2. Future research into the complex interaction between the CNS and the immune system following cortical injury will offer novel insight into the progression of acute and chronic MS. Especially as current DMTs cannot pass the blood-brain barrier directly if it is undamaged, novel methods to allow therapeutic intervention within the CNS via direct route may offer promising treatment alternatives. There are exciting research studies and clinical trials underway that will help clarify the cause of MS. Through a greater understanding of the interaction between the immune system and the CNS, researchers will continue to fill the gaps in understanding this complex disease.

References +

Magliozzi R., Howell O. W., Calabrese M., Reynolds R. Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis. Nature Reviews Neurology. 2023. https://doi.org/10.1038/s41582-023-00838-7

Zuroff L. R.; Benjamins J. A.; Bar-Or A.; Lisak R. P. Inflammatory mechanisms underlying cortical injury in progressive multiple sclerosis. Neurosciences. 2021, 8, 111. http://dx.doi.org/10.20517/2347-8659.2020.35

Gelfand J. M., Cree B. A. C., Hauser S. L. Ocrelizumab and Other CD20+ B-Cell-Depleting Therapies in Multiple Sclerosis. Neurotherapeutics. 2017. https://doi.org/10.1007/s13311-017-0557-4

Cotchett K. R., Dittel B. N., Obeidat A. Z. Comparison of the Efficacy and Safety of Anti-CD20 B Cells Depleting Drugs in Multiple Sclerosis. Multiple Sclerosis Related Disorders. 2021. https://doi.org/10.1016/j.msard.2021.102787

Pender M. P., Csurhes P. A., Smith C., Douglas N. L., Neller M. A., Matthews K. K., Beagley L., Rehan S., Crooks P., Hopkins T. J., Blum S., Green K. A., Ionnides Z. A., Swayne A., Aftab B. T., Hooper K. D., Burrows S. R., Thompson K. M., Coulthard A., Khanna R. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. JCI Insight. 2018. https://doi.org/10.1172/jci.insight.124714

Altieri C., Speranza B., Corbo M. R., Sinigaglia M., Bevilacqua A. Gut-Microbiota, and Multiple Sclerosis: Background, Evidence, and Perspectives. Nutrients. 2023. https://doi.org/10.3390/nu15040942