Role of Biomarkers in MS ResearchACCELERATE THE NEXT GENERATION OF MS TREATMENTS
Why Biomarkers Are Critical to MS Research
A biomarker is a biological sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Currently, MRI scans are the only biomarker – or measurement – used in MS research. But MRIs cannot accurately measure if a treatment truly promotes myelin repair, which represents the next generation of MS treatments.
To accelerate the development of new treatments, MRF is focused on identifying additional biomarkers that can be assessed via blood tests – which are faster, less invasive, lower cost and more specific than MRI. These new biomarkers will benefit the millions worldwide living with MS by enabling smaller and faster clinical trials.
MRF Biomarker Research
March 2024
MRF funds a follow-on study at the University of Barcelona of astrocyte-derived extracellular vesicles. Astrocytes are thought to be critical for feeding both neurons and oligodendrocytes as well as creating a local environment in the brain that is conducive for repair.
February 2024
MRF begins a study of human CNS-endothelial cells and oligodendrocytes to determine the specific molecular signature of ETX-induced EV secretion in MS patients. Such a signature would generate a novel diagnostic tool and would help generate new therapeutic targets to inhibit and repair both ETX-induced BBB permeability and demyelination.
November 2023
MRF initiates a study at the Montreal Neurological Institute to identify the EV signatures, derived from microRNAs, from damaged / stressed oligodendrocytes and neurons. This will potentially lead to the discovery of clinically relevant biomarkers of disease progression.
September 2023
MRF funds development of reproducible assays to obtain cell type-enriched EVs from oligodendrocytes, neurons, astrocytes, and CNS-endothelial cells isolated from blood samples to access their EV cargo as indicators of myelin repair. Subsequent validation and optimization of these assays would then provide an analytic pipeline of characterized CNS, cell-specific EVs for drug development programs.
June 2023
Building upon MRF’s EV research results, MRF funds new assay development in Switzerland to increase the throughput of oligodendrocyte and astrocyte EV isolation and analysis from blood samples.
May 2023
MRF funds a new research project at Johns Hopkins University to image the iron laden microglia in the rim of chronic active MS lesions as a biomarker of remyelination or neuroprotection.
May 2023
MRF enters into a collaboration with NanoSomiX to use their technology to evaluate plasma-derived neuronal and oligodendrocyte EVs as biomarkers.
Nov 2022
Katie Whartenby, PhD, joins MRF’s research staff. For the last two decades, Katie had a lab at Johns Hopkins University focused on understanding autoimmune responses in MS.
May 2022
MRF initiates a study at Columbia University to use EVs to develop new ways to check microglial activity in various sub-types of MS patients. (In MS patients, destruction of myelin in the CNS is associated with activated microglia.)
President’s Letter
Dear Friends and Supporters of MRF,
As you know, our final MRF goal is to have pharma widely use our biomarker to facilitate the development of therapeutics that promote repair/remyelination in MS. We’re close to meeting this goal, thanks to your generous support, however we have more work to do to get over the finish line.
First, I’d like to share the excitement of the initial pharma executives who have seen our results to date. These are excerpts from emails we’ve received from three pharmaceutical company executives who are driving myelin repair drug development programs and will most benefit from a biomarker. (Company names and program details have been removed to preserve confidentiality; bolding added.)
“We do not have biomarkers to help us develop new therapies that will promote repair and stop progression in MS. Not having biomarkers makes trying to develop these kinds of therapies very very risky. We have been following the work of MRF and applaud your scientific strategy and, while knowing that developing a blood-based assay for extracellular vesicles generated from CNS cells (neurons, etc.) is difficult, the payoff for being able to develop remyelinating drugs is huge. In fact, we are anxiously waiting for MRF to tell us that the assay being developed is ready for clinical trial samples.”
“The projects that MRF supports is research that is desperately needed if we are to develop new therapies designed to address the progression and demyelination in MS.
“My group is developing new therapies for MS; particularly those that stop the destructive processes that lead to progression and those that can lead to repair/remyelination. Most of the endpoints that are currently available to assess new drugs in our clinical trials are relatively slow and insensitive. There is an urgent need for biomarkers that reflect the more dynamic cellular processes. Assuming the assays for these biomarkers are reliable, they will likely facilitate the development of drugs to prevent disability progression and promote repair in MS.
“MRF is the only MS-focused non-profit that has really focused on developing biomarkers (with a strong program on extracellular vesicles) to enable drug development. The idea that extracellular vesicles from the CNS may be a ‘liquid biopsy’ of the state of brain cells is extremely compelling. This would allow the development of promising therapeutics with greater understanding and confidence.
“In fact, I am sufficiently intrigued and hopeful about the MRF approach that I have initiated a pathway for us to share some of our clinical trial samples with an MRF sponsored lab to assess the utility of their assays.
“One extra note: if reliable assays for brain derived EVs are developed, this approach could be extremely useful in other neurological diseases including ALS, Alzheimer’s disease and Parkinson’s disease.”
“We are planning a first in human study to treat patients who have progressive multiple sclerosis with an engineered … cell therapy. We are targeting the compartmentalized inflammation in the brain that we believe drives progression independent of relapse activity in MS.
“Biomarkers are sorely needed to understand the effect of all MS directed therapies in the central nervous system (CNS) including ours. We need a way to understand the effect of … on neuroinflammation, neurodegeneration and myelination in the CNS through blood-based biomarkers.
“We find the extracellular vesicle (EV) work sponsored by the Myelin Repair Foundation particularly intriguing since it has the potential to measure changes in the biology of astrocytes and neurons without a lumbar puncture.
“We will be positioned to test EVs from patient samples from our Phase 1b in your assay labs when available.”
The entire MRF team is pleased and motivated by the progress we have made and the implications for accelerating myelin repair treatments to MS patients that can’t afford to wait. To meet our final goal are now focused on further validation and testing initial samples from pharma. Your support is needed for us to complete this critical endeavor! Please donate today.
“Although hundreds of thousands of scholarly scientific articles are published every year, the FDA approves less than two-dozen new drugs a year. What's missing is the translation of all that cutting-edge science into cutting-edge cures. That's where the MRF comes in.”
Scott Cook, Co-Founder, Intuit
“The Myelin Repair Foundation's model—which brings together researchers and works to ensure that their work is relevant to development of patient treatments—is a critical innovation at a time when our system of drug development is looking for new ideas.”
Elliot Gerson, Aspen Institute and Rhodes Trust
“There are many foundations funding research on different diseases, but fewer that are investing in the infrastructure to manage that research more effectively.”
Nancy Barrand, Special Advisor for Program Development, Robert Wood Johnson Foundation
“Innovation is a decidedly social process encompassing diverse individuals, corporations, communities, networks, and regions. The work of the Myelin Repair Foundation is an excellent demonstration of these principles.”
John Hagel, Co-Chair, Deloitte LLC, Center for Edge Innovation
“I am drawn to new ideas that have the potential to change a market. I am inspired by the MRF's business model and advanced medical research concepts. MRF is a non-profit, but it breaks every rule and barrier to the speed of a start-up with the agility of a successful business.”
Samantha Fein, Managing Director, Threxy
“Unlike a lot of other organizations, the Myelin Repair Foundation really understands the intersection between academia and pharma. And if you're going to make a difference in MS, myelin repair is where you're going to have to put your efforts. We are putting efforts there.”
Craig Sorensen, Vice President, Vertex Pharmaceuticals
“Working with MRF is an unmistakable path for me to bring effective therapeutics — and new hope — for all patients in need.”
Beatrice Perotti, Ph.D., M.B.A., President and CEO, Beatrice Perotti, Inc.
“Breaking down barriers between academic research and commercial drug development will be the centerpiece of the Myelin Repair Foundation's legacy.”
William K. Bowes. Jr., Founder Amgen, U.S. Venture Partners
“Through our funding, we look for ways to make medical research more relevant to health improvement. MRF's leadership in transforming the research paradigm is very compelling to us.”
Lynne Garner, Trustee & President, Donaghue Foundation
“We view the Myelin Repair Foundation's Accelerated Research Collaboration model as just that, a transformative idea with the potential to pioneer a new approach to medical research that can speed the discovery process and lead to the development of new treatments.”
Carl Schramm, President and CEO, Ewing Marion Kauffman Foundation
“Not enough progress has been made, fast enough, toward effective treatments for MS. I am involved with the Myelin Repair Foundation because I really believe in the methodology: Getting the best people together to solve a really tough problem collaboratively. I truly believe that the Myelin Repair Foundation offers real hope.”
Julie Wainwright, Founder and CEO, SmartNow.com
“MRF's collaborative model is … definitely accelerating results. The scientists have made important advances that, if the labs had been working on their own, would have been much less likely.”
Brian Popko, Ph.D., University of Chicago, Director, Jack Miller Center for Peripheral Neuropathy, Associate Chair for Research, Department of Neurology
“I support the MRF for two reasons. Personally, I have a connection to MS: My husband has MS. But even beyond that, the vision of Myelin Repair Foundation and the method that they are proving out to get drugs to people faster is a really big vision that is important for a lot of unmet medical needs and it is exciting to be a part of it.”
Sharon Wienbar, Managing Partner, Scale Venture Partners
“If you just leave it to basic scientists working alone in their own labs, converting basic scientific discoveries into drugs almost never happens. Without the ARC model there is no infrastructure for accelerating drug development.”
Ben Barres, M.D., Ph.D., Stanford University School of Medicine, Chair, Neurobiology Department
“Disease foundations play an important role in funding early stages of research when other research and investment dollars are scarce. I am impressed by what the Myelin Repair Foundation is doing to encourage collaboration. MRF's model is novel and spot-on in terms of moving innovative research forward.”
Gail Maderis, President and CEO, BayBio: Northern California's Life Science Association
“The Myelin Repair Foundation has identified the best labs in a defined area and brought them together with excellent and independent minds from the pharmaceutical industry to advance the most promising ideas for novel therapeutics.”
Martin Raff, M.D., Emeritus Professor, University College London
“Collaborative innovation — bringing together people from different disciplines, with complementary skills — is a powerful strategy for solving complex problems. The MRF's model provides important lessons for the pharmaceutical industry, which faces a crisis of innovation in developing treatments for complex diseases.”
Karim R. Lakhani, Harvard Business School
“Not enough progress has been made, fast enough, toward effective treatments for MS. I am involved with the MRF because I really believe in the methodology: Getting the best people together to solve a really tough problem collaboratively. I truly believe that the MRF offers real hope.”
Ted Yednock, Executive Vice President, Head of Global Research, Elan Pharmaceuticals
“I believe the most striking accomplishment has been the success of the model. The thought that one could get several excellent basic scientists to work in a united effort with a clinical target in mind is really impressive... Not only has the group worked together, but there are now products of this effort. Very impressive!
Henry F. McFarland, M.D. (Ret.), National Institutes of Health