Charcot Award 2021: Progressive MS, a personal perspective

The 2021 Charcot Award was awarded to Prof. Alan J. Thompson (University College London, UK). “The Charcot Award is viewed by the MS community as the ultimate accolade for a lifetime’s work, and I’m absolutely delighted to be the 2021 recipient,” Prof. Thompson said. As part of this honour, Prof. Thompson gave the Charcot Lecture at the ECTRIMS 2021 meeting [1].

“Approximately 1 to 1.5 million people are currently suffering from progressive forms of MS worldwide,” Prof. Thompson started his lecture. “The increasing disability, reduced quality of life, and costs for the individual and the community that are a result of this condition demonstrate the need to focus on progressive MS.” Prof. Thompson argued that most therapies in the last 3 decades were developed for relapsing-remitting MS, leaving progressive MS underexposed. “In primary progressive MS, ocrelizumab is the only effective therapy that has been developed in the last 30 years. Fortunately, in recent years the international focus has been shifting towards progressive MS.”

Prof. Thompson emphasised that the key to developing effective therapies lies in understanding the injury mechanisms driving progression. “Studies into slowly expanding lesions [2,3] taught us that progression is largely independent of relapse. Moreover, we have learned that neurodegeneration starts before MS is clinically manifested. The current clinical course descriptors are not necessarily reflecting what is happening pathologically. Therefore, therapies should be initiated before symptoms or progression of symptoms are clinically present.” In addition, Prof. Thompson mentioned that research in progressive MS should focus on how to match clinical descriptors with underlying pathological mechanisms.

Machine learning has shown value in this aspect, according to Prof. Thompson. A machine learning model was able to differentiate between MS subtypes (cortex-led, normal-appearing white matter-led, lesion-led) based on MRI data. These subtypes were predictive of treatment response and thus providing clinical benefits [4]. Prof. Thompson stressed that MRI markers are needed for the early stages of the disease. “If we initiate treatment after compensatory mechanisms collapse and biological ageing exerts its influence on patients, it is probably too late.”

Prof. Thompson continued by addressing drug targets in MS. “The majority of drugs in MS have an immune-modifying effect. We should focus more on remyelination and neuroprotection in progressive MS.” The REBUILT trial (NCT02040298) and the SPRINT-MS trial (NCT01982942) are 2 recent trials that showed efficacy of this approach in patients with MS. “I believe we should continue to develop and investigate neuroprotective and remyelinating agents in the future.”

Concluding his lecture, Prof. Thompson expressed his hope for the future: “the International Progressive MS Alliance puts effort into understanding the mechanisms behind progression in MS, accelerating clinical trials, and enhancing the quality of life of patients with progressive MS. If we continue this hard work, I hope we can establish early initiation of effective therapies in order to prevent progressive MS from arising.”

1. Thompson AJ. Charcot award 2021: Progressive MS, a personal perspective. Plenary Session 2, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Absinta M, et al. JAMA Neurol. 2019;76(12):1474–1483.
3. Calvi A, et al. Mult Scler, Sep 23, 2020. DOI: 10.1177/1352458520958589.
4. Eshagi A, et al. Nature Commun. 2021;12(1):2078.

 

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Posted on 9 December 202125 March 2024