Research Trends

Our understanding of the pathogenesis of MS has expanded considerably in recent decades. We have seen a shift towards a more complex picture of MS, as a disease involving a variety of immunopathogenic mechanisms with pathology affecting both white and gray matter in the brain. Current basic research in MS continues to clarify the complex pathobiology of the disease, with the goal of improved diagnosis, treatment, and prevention.

Although we are making advances in our understanding of MS, gaps in understanding pose major challenges to improved treatment of MS. We still do not understand the cause(s) of MS nor have a complete picture of the pathogenesis of the disease. The effectiveness of currently available disease-modifying treatments is limited, and we do not understand the reasons behind treatment failure in patients who fail to respond or lose response to available medications. Additionally, treatment options for progressive MS remain limited.

Despite all of this, at this time, there are currently more MS treatments approved and on the market, as well as in development, than ever before, making MS research an exciting and innovative area of study.1

Goals of basic research in MS

Depending on who you ask, the goals of MS-related research may vary. Overall, the main trends within the MS research landscape are to restore damage that has been caused by MS, to stop the progression of MS, and to reduce the prevalence of MS altogether (either by finding ways to reduce an individual’s risk of developing the condition, or by curing the condition in those who already have it).1

Research tools

A variety of tools are used in MS research. These include high-throughput genetic screening techniques, animal modules of MS, methods for molecular analysis, flow cytometry methods for examining functional and surface features of neural and immune cells, cell culture methods for modeling interactions between neural and immune cells, techniques for measuring and assessing soluble factors including neurotransmitters, cytokines, chemokines, hormones, and growth factors, neuroimaging techniques, techniques for the collection and cultivation of adult stem cells, and histopathological and microscopic methods.1-3

Key research questions in MS

MS affects two systems in the body, the CNS (including the brain, optic nerves, and spine) and the immune system. Each of these is subject to a number of influencing factors that may contribute to dysfunction, including genetics, the environment, and gender. Basic research in MS tends to focus on the two systems where MS appears, and looks at different factors that may contribute to and influence MS progression. The research questions below represent some of the main areas of ongoing research in MS.1-4

Where does the primary injury in MS occur, in the CNS or elsewhere?

This question seeks to determine whether MS stems from a defect in myelin or its precursors in the CNS, followed by secondary damage from a dysfunctional immune system. Since it is very difficult to examine tissues affected by MS at its earliest stages of development, obtaining an answer to this question poses a difficult challenge.

What structural or functional defects in myelin or its precursors contribute to MS?

This question seeks to determine the nature of the defects in myelin that allow MS to develop. There is a growing body of research investigating structural and functional characteristics of myelin in patients with MS. Studies have suggested that myelin in individuals with MS may be less mature than in non-MS individuals and that this lack of maturity may increase susceptibility for MS. Studies have also focused on the structure of the proteins that make up myelin (eg, myelin-specific protein) in MS patients and how structural changes may interact with immune system cells in MS. Other studies have examined how defects in oligodendrocytes, the CNS cells that create myelin, may play a role in inducing immune responses in MS.

If MS is associated with defects in myelin, what extrinsic exposure triggers the immune response in MS?

This question addresses possible factors outside of the body that may trigger the autoimmune response in MS, including viruses and other environmental factors. To date research in this area has implicated multiple environmental factors that appear to increase susceptibility to MS. One potential extrinsic factor that has received attention in the past several years is our diet, and its effect on the composition and characteristics of the gut biome. This then drives research further into the impact of the bacteria in our gut and the development and progression of MS. Some experts and studies suggest that the body’s immune system and its functioning are related to the types of bacteria that are present in our digestive system. Learning how the bacterial composition of the gut potentially impacts MS may lead to new, effective treatment options and patterns of eating that focus on creating and maintaining the most appropriate internal environment.5

What causes axonal damage and neuronal death in MS?

Research has examined a variety of molecular mechanisms that may contribute to axonal dysfunction, eventually leading to nerve death in MS. These include intrinsic myelin dysfunction that increases susceptibility for demyelination, immune processes causing inflammation following demyelination, and damage to mitochondria. This is a particularly important area of research, because increased understanding of the molecular mechanisms behind axonal damage may lead to new treatment strategies for protecting against nerve damage in MS.

How is myelin repair limited in MS?

A number of ongoing research efforts seek to determine why normal myelin formation and repair (via oligodendrocytes) fails to occur in MS. Studies have examined deficits in signaling between damaged axons and oligodendrocytes, defects in cells that develop into oligodendrocytes, and defects in regulatory molecules that guide oligodendrocyte development and function. Other studies have examined the effect of the pro-inflammatory environment in MS on oligodendrocyte myelin repair function.

What is the nature of immune dysfunction in MS?

A large body of research has examined the process of immune dysfunction in MS and has identified a number of different immune cell types that play a role in promoting inflammation in MS, including interleukin-17–producing T-cells, myelin-specific CD8+ T-cells, and natural killer (NKT) T-cells. Other studies have focused on the role of a range of regulatory T-cells (Tregs) in the dysfunctional regulatory environment that characterize autoimmune diseases like MS.

What role do factors including genes, environment, and gender have on immune dysfunction in MS?

Although the cause of MS remains unclear, a large ongoing research effort seeks to determine the role of factors including genes, environmental triggers, and gender in MS. Evidence from twin studies strongly suggests a genetic component to MS and results from genome-wide studies have linked multiple genetic abnormalities to increased MS susceptibility. Studies of possible environmental triggers for MS have implicated low levels of vitamin D and decreased sunlight exposure in development of MS. A number of studies have examined potential viral triggers in MS (eg, Epstein-Barr virus).1 However, there have been no definitive results to date from this line of research.

What kinds of therapies are in the works for MS?

Progress within MS research over the past few years has been exciting. In 2017, the first treatment for both PPMS and RRMS was approved by the FDA (Ocrelizumab), and studies surrounding the use of adult stem cells as a treatment option for MS are underway with promising results.6-10 Additionally, gene therapy techniques, which are in their infancy in relation to MS and its treatment, have showed promising preliminary results in animals.11 Gene therapy attempts to replace mutated genes in the body with a healthy copy, introduce new genes into the body that may help fight against an actively occurring condition, or knock out a gene that is not working in the way that it should.12 Studies on combination therapies for MS are also being pursued, and deeper dives into the human genome to determine which genes or biomarkers are related to MS development and progression are also flourishing.13,14

Overall, MS research is growing and our understanding of the condition and what factors may cause it are getting stronger. Although the research pipeline may be a slow and steady process, the results that are currently being cultivated promise for a dynamic, and hopefully, more effective treatment landscape ahead.

Written by: Casey Hribar | Last reviewed: August 2018.
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