The damage caused to neurons during Multiple Sclerosis (MS) relapses makes the disease difficult to manage. Inflammatory stages of MS are treated using corticosteroids and disease modifying therapies (DMTs) (1). This relapsing remitting stage of MS also extends to the beginning stages of progressive MS which ultimately results in neurodegenerative symptoms caused by the deterioration of neurons (2,3).
This immune mediated disease has accelerated in prevalence and now resides amongst 50-300 patients within a 100,000 population (3,4). Recent advancements in medicine have led to the development of immunotherapy treatments which target chronic inflammation and reduce MS relapses (5). Whilst DMTs have revolutionised the panorama for relapsing remitting MS, there remains an unmet medical need for an efficacious, safe and well-tolerated treatment for progressive MS — one that can effectively preserve and regenerate axonal and neuronal damage (6). A variety of research avenues, both clinical and preclinical, have been explored for progressive MS, opening new lines of enquiry — one of which is remyelination therapy (3,7,8).
Remyelination is the regeneration of the myelin sheath surrounding nerve cells and is associated with functional recovery. Typically, this lipid rich substance is produced by oligodendrocytes. For remyelination to occur, nerve fibres are required to remain intact for oligodendrocyte cell recognition (9). However, this often isn’t the case in progressive MS patients, as neurons can deteriorate irreversibly due to oxidative damage (10). Although remyelination therapy may not fully address the need in managing progressive MS, it does pose promising alternatives in both relapsing remitting and the early stages of progressive MS.
Over recent years, research has identified several therapeutic targets that enhance remyelination, stimulating endogenous progenitor cells thereby reducing chronic axonal loss (11). For example, the retinoid X receptor-γ (RXRγ) is a nuclear receptor which plays an important role in regulatory mechanisms by enhancing oligodendrocyte progenitor cell (OPC) differentiation into oligodendrocytes, which produce myelin (12). Although RXR agonists are primarily used to treat certain cancers and metabolic disorders, they have previously been shown to enhance remyelination, induce OPC differentiation and improve neuroprotection in animals, which may identify them as a potential target for future MS treatments (11).
Various clinical trials are currently underway to investigate the effects of RXR agonists in MS patients. Researchers at Cambridge University and Edinburgh showed promising outcomes in a phase 2a trial targeting the RXRγ receptor in relapsing remitting patients. (13)
At The Corpus, we specialise in developing and delivering virtual medical education meetings. Our goal of these meetings is to better equip healthcare professionals in managing unmet educational needs in their therapy areas. Our expert led programmes are filled with world renowned specialists who deliver engaging content, followed by interactive discussions.
We are currently developing a new MS programme which will include a focus on remyelination therapy. If you would like to find out more about how you can support programmes such as this, or any other therapy area then please contact us at communications@the-corpus.com.
References:
-
Plemel, J.R., Liu, W.Q. and Yong, V.W., 2017. Remyelination therapies: a new direction and challenge in multiple sclerosis. Nature reviews Drug discovery, 16(9), p.617.
-
Kim, H.K., Park, S.K., Zhou, J.L., Taglialatela, G., Chung, K., Coggeshall, R.E. and Chung, J.M., 2004. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain, 111(1-2), pp.116-124.
-
Lubetzki, C., Zalc, B., Williams, A., Stadelmann, C. and Stankoff, B., 2020. Remyelination in multiple sclerosis: from basic science to clinical translation. The Lancet Neurology, 19(8), pp.678-688.
-
Thompson, A., Baranzini, S., Geurts, J., Hemmer, B. and Ciccarelli, O., 2018. Multiple sclerosis. The Lancet, 391(10130), pp.1622-1636.
-
Cross, A.H. and Naismith, R.T., 2014. Established and novel disease‐modifying treatments in multiple sclerosis. Journal of internal medicine, 275(4), pp.350-363.
-
https://mstrust.org.uk/a-z/neuroprotection accessed 10 February 2021
-
https://mstrust.org.uk/news/remyelination-research-what-it-means-people-ms accessed 10 February 2021
-
Brück, W., Kuhlmann, T. and Stadelmann, C., 2003. Remyelination in multiple sclerosis. Journal of the neurological sciences, 206(2), pp.181-185.
-
Lassmann, H., 2018. Multiple sclerosis pathology. Cold Spring Harbor perspectives in medicine, 8(3), p.a028936.
-
Franklin, R.J., Edgar, J.M. and Smith, K.J., 2012. Neuroprotection and repair in multiple sclerosis. Nature Reviews Neurology, 8(11), pp.624-634.
-
Huang, J.K., Jarjour, A.A., Oumesmar, B.N., Kerninon, C., Williams, A., Krezel, W., Kagechika, H., Bauer, J., Zhao, C., Baron-Van Evercooren, A. and Chambon, P., 2011. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nature neuroscience, 14(1), pp.45-53.
-
Aboul-Enein, F. and Lassmann, H., 2005. Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?. Acta neuropathologica, 109(1), pp.49-55.
-
https://msvirtual2020.org/wp-content/uploads/2020/09/LB01.02.pdf accessed 10 February 2021