These articles discuss many of the roadblocks that have slowed research into progressive MS in the past, with a focus on finding solutions and identifying new ways forward in order to accelerate outcomes for people with this type of MS. In particular, they highlight the International Progressive MS Alliance as a valuable means for prioritising progressive MS within the global research agenda. MS Research Australia is a managing member of the Alliance, contributing $1.1 million over six years to the Alliance research projects.
In this series of articles, the authors consider a range of issues relevant to the growing research drive towards a solution for progressive MS. The authors review the current knowledge and make specific recommendations for the most promising avenues to make real progress in understanding the mechanisms of progressive MS, conducting more effective clinical trials, and finding better ways to manage symptoms.
In two expert commentary articles, key MS experts and advocates provided some insights into the more important areas for future focus in studying progressive MS. In the first editorial, Dr Timothy Coetzee from the National MS Society in the USA, Dr Paola Zaratin from the Italian MS Foundation, and Mr Trevis Gleason, an MS advocate from Ireland, highlight the key barriers that need to be overcome for progressive MS, including the availability of dedicated research funding, facilitating global research collaboration, and ensuring regulatory bodies are equipped to understand the different trial designs needed to test new therapies for progressive MS.
In the second editorial, Professor Alan Thompson from University College London commented that “Every time a new treatment for [relapsing-remitting MS] comes on the market, it serves to remind people with progressive MS that they are still waiting…” Professor Thompson reiterates that there are two key questions needing to be answered before we can make any progress in finding treatments for progressive MS: first, understanding the biological mechanisms of progression, and second, designing innovative and effective clinical trials. Professor Thompson is the Chair of the International Progressive MS Alliance Scientific Steering Committee, which is a global platform dedicated to answering these questions through targeted research funding.
In the same issue of Lancet Neurology, a series of research review articles was also published that highlight three key areas of study into progressive MS: understanding the biological mechanisms, identifying symptom-management therapies, and designing effective clinical trials.
International researchers Dr Mahad from the University of Edinburgh, Dr Trapp from the Lerner Research Institute in the USA, and Dr Lassmann from the Medical Research Institute of Vienna, Austria, reviewed the current literature studying the biological mechanisms underlying disease progression. The authors suggest that the early stages of inflammation in relapsing MS may trigger a cascade of events leading to the accumulation of damage and degeneration, which are amplified by age-related processes also causing damage. The authors identify several key elements that may be driving the accumulation of damage, including the involvement of microglia cells (immune cells in the brain), chronic oxidative injury from ‘free radicals’, age-related iron accumulation in nerve cells, and damage to the components of nerve cells’ machinery that drives energy production.
Dr Anthony Feinstein from the University of Toronto, Dr Jenny Freeman from Plymouth University, and Dr Albert Lo from Brown University have worked together to review the published clinical trials of symptom-management treatments that have been tested in people with progressive MS. The authors note that very few trials have been specifically dedicated to studying progressive MS, which makes conclusions difficult regarding the effectiveness of current rehabilitation methods and therapies for alleviating symptoms of progression. They suggest that future trials could look at testing multiple therapies in a controlled environment, to expedite trial outcomes.
Extending on the above article, Dr Ontaneda and Dr Fox from the Mellen Center for MS Treatment and Research in the USA, and Dr Chataway from University College London undertook a review of clinical trial methodology that has been used to study progressive MS to date. The majority of these trials, testing disease-modifying therapies for progressive MS, have shown disappointing results. This article makes recommendations for the most effective protocol design for future clinical trials, and the best tools that can be used to measure treatment efficacy and disease progression. They suggest that trials need to be conducted over a longer period of time, using specialised biological tests and advanced techniques for brain imaging to evaluate treatment response and determine trial outcomes with greater sensitivity.
While these reviews articles serve to reiterate much of the already-published literature, it is never-the-less crucial to see these opinions of key international MS researchers brought together for contemplation one place. This allows for concrete recommendations and focusses the research community on the crucial steps forward for research into progressive MS. These review papers will serve as a cornerstone for new trials currently under development that are aiming to establish gold-standard methodologies for measuring disease progression and evaluate treatment efficacy in people with progressive MS.
