Multi-million dollar grants announced at ECTRIMS by the International Progressive MS Alliance marks major milestone in progressive MS research

alliance

Professor Alan Thompson announces the recipients of the International Progressive MS Alliance Collaborative Network Awards at ECTRIMS

How quickly time flies. A little over a year ago, the MS Society announced the recipients of the International Progressive MS Alliance planning awards, the first step in an unprecedented global effort designed to forge collaborations between people of all research backgrounds and scientific expertise around the world, who together have the capacity to speed up the development of treatments for progressive MS. Each of the 11 grant recipients developed proposals for larger-scale projects aimed at addressing the most complex scientific and healthcare challenges in progressive MS. The proposals were submitted for another round of reviews, after which three projects would be selected for €4.2 million (or $6 million) in funding.

Today at an ECTRIMS press conference, The Alliance announced the successful awardees of the €4.2 million Collaborative Network Award grants. The three selected multi-national research networks will tackle critical gaps facing progressive MS research, including the development of effective drugs for countering disease progression, the discovery of new biomarkers that can help researchers measure progression and the response to treatments, and the design of faster and smaller clinical trials that will cut down on the time needed to bring new therapies from the drawing board to people living with MS.

I’m happy to note that one the grant recipients is from Canada: Dr. Douglas Arnold from the Montreal Neurological Institute at McGill University. Additionally, several other Canadian researchers were among the collaborators listed for all three grants, including Dr. Jack Antel from McGill University and Dr. Alexandre Prat from the University of Montreal.

Read on for descriptions of the selected studies.

A new generation of MRI biomarker for disability progression for use in clinical trials

One of the issues hampering the development of therapies for progressive MS is that researchers still don’t have a good sense of what to look for when measuring how participants respond to a drug in clinical trials. Establishing a good indicator for treatment success is especially important in phase II trials where researchers are trying to determine if the drug produces any sort of effect. Indicators which can be measures include clinical measures (how a person is doing symptom wise), imaging markers, or biological markers in the body.

Dr. Doug Arnold, who is regarded as one of the world’s foremost experts in advanced imaging for MS, has brought together an interdisciplinary team with the goal of developing next generation magnetic resonance imaging (MRI) markers of disease progression that can be used in early stage clinical trials. Changes in disability in people living with progressive MS that are measured in the clinic can often take time to manifest or are difficult to detect, and these subtle changes aren’t necessarily reflective of the injury to the brain that’s taking place behind the scenes.

Using cutting-edge computer science tools, ‘deep learning’ (the same technology used for facial recognition) and a rich archive of existing MRI scans (including data from 2,000 patients and 40,000 MRI scans), Dr. Arnold will take a deep look into the brains of people living with progressive MS to detect patterns that:

  1. Change over short periods of time and thus can be measured easily and quickly
  2. Are associated with changes in disability and thus can predict progression;
  3. Can tell us about the effects of a treatment on neurodegeneration and resulting disability that the person experiences.

Dr. Arnold’s research has enormous potential for multiple applications, including how clinicians diagnose progressive MS, monitor changes in disease, and assess treatment benefits. At the press release he talked about the potential for the biomarker to be translated to a quantitative measurement (a score) that can be used to assess a person’s level of disability and whether it is worsening or improving over time and before and after treatment. He also discussed the importance of involving people living with MS throughout the process of designing the study, as it helped to inform the impact of the study and its relevance to real-world experiences.

The other two grant recipients are Dr. Gianvito Martino from San Raffaele Hospital in Milan and Dr. Francisco Quintana from Brigham and Women’s Hospital in Boston.

Using computer-based tools to discover promising new drugs for progressive MS

Finding safe and effective therapies for progressive MS can often feel like searching for a needle in a haystack. Just like information science and “big data” are transforming the way we live and work, the field of bioinformatics – which combines computer sciences, statistics and engineering – is transforming the way in which new drugs are discovered (and existing drugs are reapplied to new diseases) and translated into the clinic.

Taking a brand new drug from the laboratory to the clinic can take upwards of 15 years and $1 billion, and approaches that take existing drugs approved for other diseases and ‘repurpose’ them for MS is a promising strategy for finding treatments for people living with progressive MS. We heard from Dr. Martino that this process needs to happen faster and people living with progressive MS cannot wait any longer for treatments. With the joint efforts of laboratories from five different countries, he will use sophisticated technology to pinpoint compounds that are already available and that have the potential to treat progressive forms of MS. First, Dr. Martino’s team will comb through large data sets of biological and chemical information and identify potential drugs that are linked to disease pathways underlying MS progression. Next, the team will be able to test these drug candidates in cells to see how effective they are in protecting nerve cells from damage or promoting myelin repair – two processes that play an important role in countering disease progression. After narrowing down the list of compounds to the most promising drug candidates, the team will use animals with a progressive MS-like disease to test whether these drug candidates have the potential to be effective therapies.

Dr. Martino hopes that within four years from the start of the project, his team will be able to home in on a small handful of promising drug candidates that can be taken into early stage clinical trials in people living with progressive MS.

Development of a drug discovery pipeline for progressive MS

The “innate” immune system is the body’s first-line of defense against infection; while adaptive immunity (including white blood cells like T cells and B cells) has historically dominated the conversation about MS disease mechanisms and treatments, emerging evidence is showing that problems with innate immunity can play a role in driving the disease process. Dr. Quintana and his team have recently mapped out some of the biological pathways that control the innate immune response, and they found that genetically tweaking these pathways in animals with an MS-like disease can halt damage to nerve cells and dampen progression of disability. The missing link is that there is a lack of promising candidate drugs that can target these innate immune system pathways.

With this new funding from The Alliance, Dr. Quintana’s team will take their findings to the next level with the ambitious but achievable goal of identifying drug candidates that target the innate immune system that will be ready for early stage clinical trials in people living with progressive MS within 4 years. Much like Dr. Martino’s project, Dr. Quintana will lean heavily on already approved drugs for other diseases whose mechanisms and safety profiles are known rather than “re-inventing the wheel” to ensure that promising drug candidates for progressive MS are available sooner.

What is most interesting about these project is their involvement of extensive research networks and collaboration with pharmaceutical companies. Pharma is an important link in that they have resources that can be tapped into by the academic community and they have important knowledge about how treatments are developed, tested in clinical trials, and brought to market.

We heard today from Caroline Sincock, a community member of The Alliance’s Scientific Steering Committee and person living with secondary progressive MS. It was great to hear her perspective on the studies that were awarded and work of The Alliance. She said that she was “inspired by the commitment of the researchers” and “sees the direct benefits of forming research collaborations”. She said that people living with progressive MS felt left out and left behind for so long, and that the impact of progressive MS goes beyond physical but is also felt emotionally, socially, financially, and significantly affects work and family relationships. She said that the work of The Alliance and today’s funding announcement brought “hope for real progress” and “demonstrated The Alliance’s role in not only funding research but raising awareness of progressive MS.” I think Caroline speaks on behalf of all people living with progressive MS and speaks to the importance of this work in bringing about real change.

We had a chance to speak to Dr. Arnold about his work and will share that interview with you all very soon!

Leave a Reply

Your email address will not be published. Required fields are marked *