The International Progressive MS Alliance is an unprecedented global collaboration of multiple sclerosis (MS) organizations, healthcare professionals, the pharmaceutical industry companies, trusts, foundations, donors and people affected by progressive MS, working together to address the unmet needs of people with progressive MS.
Two years ago, the International Progressive MS Alliance committed €12.4 million to support three promising international Collaborative Networks of researchers, with the goal of accelerating the identification and testing of new, breakthrough therapies for progressive forms of multiple sclerosis (MS).
In Spring 2019, the Alliance convened a meeting of the three Collaborative Networks to mark the mid-point of these ambitious projects and to assess the status and explore potential relationships and opportunities to accelerate activities. The meeting was hosted by the Danish MS Society and chaired by Professor Per Soelberg Sørensen, Professor Emeritus, University of Copenhagen. In addition to Alliance Executive and Scientific Steering committees, attendance at the meeting included those on the Alliance’s industry forum, persons affected by MS, Collaborative Network team members, and other researchers and guests. This meeting was an opportunity for each Collaborative Network team to provide an update on their progress. Below, we have provided a brief summary of their progress and the ongoing work of each network and the Alliance.
Protecting and Repairing the Brain
Professor Gianvito Martino, San Raffaele Hospital Milan in collaboration with 13 investigators from Italy, France, Germany, Canada and the United States are working to identify agents (potentially new drug therapies) that may protect nerve cells and/or promote nervous system repair as a potential treatment for progressive MS.
Though a series of experiments, analysis and modelling, the team rigourously assessed the potential efficacy and activity of 1,500 agents that can penetrate the blood-brain barrier and with potential activity on known repair and protection pathways to narrow it down to 32 agents classified as ‘front-runners’.
“The platform we have established is robust enough to be offered as a gold standard pipeline for drug screening in MS”, said Professor Martino.
This network is developing new tools with which to evaluate the potential of these agents and their ability to promote repair of myelin, the protective layer around nerve cells that becomes damaged in people with MS. The team is continuing their work with the identified ‘front-runner’ agents and continuing to narrow down this list in order to identify the most promising candidates for drug development.
Preventing Brain Damage
Professor Francisco Quintana, Brigham and Women’s Hospital, Harvard in collaboration with 8 investigators from the United States, Canada, Israel and Sanofi Genzyme are focused on the innate immune system within the central nervous system. They aim to identify drug candidates that may be effective therapies for progressive MS. While the innate immune system normally functions to protect the body from infections, researchers are investigating how immune cells in the nervous system might promote disease activity in MS. The network is identifying and validating biological pathways where an intervention could be developed to block harmful activities of the innate immune system and protect the brain.
The network presented their work on one of the suspected biological pathways that regulates the innate immune system and identified three drug candidates that reduce disease activity in an experimental mouse model of MS, a critical first step. The network will continue to investigate these three promising drug candidates. Additionally, the network took a different approach and screened a large library of compounds and small molecules with the potential to modify the innate immune system activity in the central nervous system. From this drug screen, they identified another drug candidate that they plan to test in a mouse model. The network is continuing to investigate multiple pathways that control the innate immune system and using sophisticated tools to understand cell populations in the central nervous system and their location which is likely playing a role in their activities and how they interact with other cells. Altogether, the network has four promising candidates that they are continuing to validate and pursue.
Predicting Prognosis Using MRI
Professor Douglas Arnold, McGill University in collaboration with 16 investigators from Canada, the Netherlands, Switzerland, United Kingdom and the United States, are working to develop the next generation of MRI imaging tools that can measure changes in the brain as MS progresses. Their hypothesis is that progressive MS may be detectable by MRI prior to its identification by physicians in a clinic. Detecting ‘markers’ of progression can provide information on whether treatments are effective and can be used to shorten the length and reduce the cost of clinical trials, thereby accelerating drug development.
Thus far, the network has gained access to data from 10,000 people from 20 MS clinical trials and patient registries. Altogether, the data includes more than 52,000 MRI scans of brain imaging data. Using the power of artificial intelligence through the application of advanced approaches in machine learning and super computers, this network is mining the wealth of data in the MRI scans to identify hidden information and patterns (or ‘markers’) related to progression in MS that the human eye may not detect.
Thus far, this team has amassed and harmonized data from 20,000 MRI scans from 3,800 participants and is continuing to refine and test various machine learning approaches in order to harness the potential power of artificial intelligence in order to identify ‘markers’ of progression.
Other Alliance Activities
In addition, the Alliance has also taken on new strategic initiatives to accelerate activities and progress. These initiatives are led by implementation planning teams drawn from the Scientific Steering committee, industry forum, global experts, and persons affected by MS.
“We will be weaving in the new initiatives and exploring relationships between the new initiatives and the existing networks,” indicated Professor Alan Thompson, Chair of the Alliance Scientific Steering Committee.
The implementation teams are focused on progressive MS in key areas to better understand progression (e.g. how to effectively conduct experimental medicine clinical trials for progressive MS), to accelerate clinical trials (optimizing fluid biomarkers and imaging & functional measures) and to enhance well-being (non-drug approaches to care).
The Alliance has made exciting progress thus far and will continue to move things forward to deliver on the goal of new treatments for progressive MS.
Scientific Steering Committee member, Jon Strum commented, “this took me back two years ago when we were announcing the Network awards. It was a highly conceptual conversation. But here we are at half circle today, and we can see so much real progress and science that’s been achieved. It is an understatement to say that this work is impressive. Progress fuels hope. This could not be a more hopeful convening about what’s being done.”
Stay tuned for future updates on the Alliance activities that will be shared in this blog. For the 2019 International Progressive MS Alliance progress report – see link.
Learn more about the International Progressive MS Alliance.