The joint annual congress of ACTRIMS and ECTRIMS took place virtually from 11-13 September 2020. Selected highlights and clinical studies on remyelination, EBV-specific immune therapies, and the prodromal phase of MS can be found in this article.
The annual ECTRIMS Congress (European Committee for Treatment and Research in Multiple Sclerosis) is the world's largest congress on basic and clinical research in multiple sclerosis (MS).
As in previous years, it was originally planned to be held in September 2020 in conjunction with the annual meeting of ACTRIMS (American Committee for Treatment and Research in Multiple Sclerosis) in Washington D.C.1 The coronary crisis led to the 'MSVirtual2020', where almost 200 leading specialists from research and clinical practice presented a somewhat streamlined program.
In case you missed it: the recorded scientific lectures and ePosters will be available on-demand (but for a fee) until the end of February 2021. We have compiled some interesting topics in this article, even though these can of course only represent a very small selection of all that was offered during the event.
Unlike other neurological diseases, such as Parkinson's disease, the existence of a prodromal phase in the context of MS has received little attention. Historically, it was not believed that the classic symptoms of MS were preceded by such a phase.
Dr. Helen Tremlett (University of British Columbia, Canada), provided convincing arguments in a keynote presentation on the possibility to detect patients with a high probability of developing MS earlier, before classic signs become clinically apparent. From their presented data, it is clear, among other things, that in the 5 years before a definitive diagnosis of MS, a significant increase in hospitalization and increased use of medical services and prescription drugs (compared to the normal population) can be observed. This is usually due to unspecified symptoms that can occur months or even up to 10 years before the onset of classic MS symptoms, such as disorders of cognition, gastrointestinal tract, skin, bladder, but also pain, depression, fatigue, headaches, or anemia.
The fact that similar prodromal phenomena occur in other autoimmune diseases, such as rheumatoid arthritis or inflammatory bowel disease, suggests autoimmune dysregulation as an underlying mechanism.2
In addition to protecting nerve fibers from damage, many studies are looking at strategies for remyelination.
One of the two main approaches is to stimulate the body's own repair processes. A speaker from France referred to a small randomized controlled trial that is just starting. Since there is experimental evidence that electrical activity in nerves stimulates myelin repair, this new study examines the effect of transorbital electrical nerve stimulation in patients after an acute optic neuritis episode, a type of myelin damage that is often the first sign of MS.3
A team from the San Raffaele Scientific Institute, Italy, showed in mice that transplanted neural stem cells can produce factors that reduce inflammation and promote myelin repair. The same team is currently conducting the first small human study. Twelve patients with progressive MS received three cell injections. To date, no serious side effects have occurred and the transplanted cells survived for at least three months. Initial observations suggest reduced signs of inflammation in the cerebrospinal fluid (CSF), but this phase of the study will initially focus on evaluating safety.4
In his presentation, Dr. Robin Franklin (Cambridge University) explained that myelin repair can fail as MS progresses and addressed why aging brains are less amenable to remyelination. His team recently found that the brain becomes more rigid with age, which can become an inhibitor for intrinsic progenitor cells involved in repair processes. In laboratory models, they tested ways to make progenitor cells fail to recognize brain stiffness, which seems to put these cells back on a repair course.4
In recent years, there has been growing evidence that the Epstein-Barr virus (EBV) plays a central role in the pathogenesis of MS.5, 6 Persistent EBV infection in the central nervous system (CNS) appears to trigger a T-cell response that is designed to eliminate the virus but inadvertently damages the CNS (often referred to as "bystander injury" effect).7
Some small studies presented at the ECTRIMS 2019 congress reported astonishing improvements after EBV-targeted T-cell immunotherapy in advanced MS patients. This year again, an exciting, small Phase I study on the treatment of progressive forms of MS was presented.4,8 In a first unblinded dose-finding phase (1 year), an increase in the dose showed an improvement in disability with good tolerability in a growing proportion of patients. Patients who achieved an improvement in disability maintained it overall in later stages and also recorded less fatigue, better physical function, and less loss of brain volume on MRI. Following these encouraging results, the multicentre trial is now entering a four-year open-label, placebo-controlled, randomized extension.
References:
1. MSVirtual2020 | Virtual Joint ACTRIMS-ECTRIMS Meeting. MSVirtual2020 https://msvirtual2020.org/.
2. Segal, B. Highlights from MSVirtual2020. Neurodiem https://www.neurodiem.de/news/highlights-from-msvirtual2020-5AAAn6E7WxwHTAdvX1BQ2i?locale=en-US.
3. Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04042363.
4. World’s Largest MS Research Conference Goes Virtual to Share Research Progress. National Multiple Sclerosis Society http://www.nationalmssociety.org/About-the-Society/News/World’s-Largest-MS-Research-Conference-Goes-Virtua.
5. Abrahamyan, S. et al. Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 91, 681–686 (2020).
6. Giovannoni, G. The cause of MS. Multiple Sclerosis Research Blog https://multiple-sclerosis-research.org/2019/10/the-cause-of-ms/ (2019).
7. Giovannoni, G. A smoking gun? Multiple Sclerosis Research Blog https://multiple-sclerosis-research.org/2019/10/a-smoking-gun/ (2019).
8. M. Pender. P0226 - Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T- cell immunotherapy for progressive forms of multiple scleros. https://msvirtual2020.org/wp-content/uploads/2020/09/P0226.pdf