- More than 70 experts convened in Lisbon, Portugal in November 2015 for an International Conference on Cell-Based Therapy for Multiple Sclerosis. “Cell-based therapy” refers to the transplantation, delivery or stimulation of various cell types for the purpose of treating MS, much of which remains in early experimental phases.
- The conference was held under the auspices of the International Advisory Committee on Clinical Trials in MS – a group jointly sponsored by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional support from the Americas Committee for Treatment and Research in MS (ACTRIMS) and the Multiple Sclerosis International Federation (MSIF).
- Cell-based therapy is being explored in MS both for turning down damaging immune responses and for promoting nervous system repair.
- Progress was reviewed related to the value of specific cell types, including hematopoietic stem cells (derived from the bone marrow), mesenchymal stem cells (derived from many different adult tissues), and oligodendrocyte precursor cells (derived from multiple sources).
- Controlled clinical trials were deemed the optimal way to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS.
- A review of the findings and consensus on next steps will be published by the conference organizers, with recommendations to help speed the development of new cell-based treatment solutions.
Over the last several years, there has been mounting progress in innovative research related to the potential of many types of stem cells both for slowing MS disease activity and for repairing damage to the nervous system. At present, there are no approved stem cell therapies for MS, and stem cell therapy is still in the experimental stage.
With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, the potential of all types of cell-based therapies is being explored. “Cell-based therapy” refers to the transplantation, delivery or stimulation of various cell types for the purpose of treating MS. To speed and coordinate this work, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened in November 2015 in Lisbon, Portugal.
The conference was held under the auspices of the International Advisory Committee on Clinical Trials in MS – a group jointly sponsored by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional support from the Americas Committee for Treatment and Research in MS (ACTRIMS) and the Multiple Sclerosis International Federation (MSIF). Conference Chairs were Jeffrey A. Cohen, MD (Cleveland Clinic, USA, also Chair of the International Advisory Committee on Clinical Trials in MS), Marcelo C. Pasquini, MD, MS (Medical College of Wisconsin, USA) and Neil Scolding, PhD, FRCP (Southmead Hospital Bristol, UK).
More than 70 experts gathered to review progress in the multiple approaches to cell-based therapy – the first conference to focus on major cell-based therapy possibilities for the treatment of MS. Topics ranged from basic biological activity and interactions of various cells, clinical trial experience and safety, future trial designs, ethics, and practical considerations such as regulatory issues and scaling up for high-volume production of therapeutic cells.
Hematopoietic stem cells (HSCT):
One type of procedure that has been explored for many years in MS is called “hematopoietic stem cell transplantation,” or HSCT. This procedure attempts to “reboot” the immune system in people with MS. Stem cells from an individual’s own bone marrow or blood are stimulated, captured and stored. Then the immune system is depleted by chemotherapy, radiation or both. The stored stem cells are then reintroduced, usually by infusion into a vein. The new stem cells migrate to the bone marrow and over time produce new cells that eventually repopulate the body with an immune system that is less likely to attack the central nervous system.
There is more experience using HSCT in MS than any other cell therapy approach. Participants heard from investigators about results from their recent and ongoing clinical trials; and about treatment protocols, different approaches to depleting the immune system, safety issues and determining outcomes. Discussion focused on current knowledge, next steps and additional studies needed to fully understand benefits and risks of HSCT in MS, and who might benefit most from this approach.
Adult Mesenchymal Stem Cells (MSC)
- Mesenchymal stem cells are adult cells found in several places in the body, including the bone marrow and fat tissue. These cells have undergone limited testing in clinical trials to reduce immune activity and to augment nervous system repair in MS. With this approach, an individual’s immune cells are not destroyed or replaced. Instead, an individual’s mesenchymal stem cells are isolated from the bone marrow, blood or other tissues and cultured in the lab to increase their purity and numbers, and then re-introduced into the body by intravenous (into the vein) or intrathecal (by spinal tap) injection. Mesenchymal stem cells have potential for turning into different types of tissues, but they are thought most likely to work by encouraging the body’s natural repair mechanisms.
Participants heard about MSC approaches in autoimmune diseases other than MS and technical issues encountered, as well as possible sources of MSCs, methods of expanding and preserving them, and safety questions such as the potential formation of unwanted tissue and cancers. Several investigators presented brief summaries of early-phase clinical studies of mesenchymal cells in MS.
Cell Therapy for Nervous System Repair:
Another approach, which hasn’t yet been tested in people with MS, focuses on repairing nervous system damage with stem cells that may replace damaged cells (oligodendrocytes) that make myelin. Myelin is the protective coating on nerve wires which is damaged during MS. Stem cells called “oligodendrocyte progenitor cells” (OPCs) reside in the brain and conduct natural repair in response to injury. These cells have been grown and expanded in lab dishes as a potential source for transplantation. Another cell source being explored involves using an individual’s own cells from skin or other tissues, which are reprogrammed to turn them into stem cells. These cells are called “induced pluripotent stem cells” or iPSC. It’s possible such cells would not be rejected by the person’s immune system after transplantation. (Read more
about other research to repair the damage in MS.)
Presentations at the conference focused on the biology of OPCs and iPSCs, their potential for transplantation, methods for growing iPSCs in the lab, and their use for screening compounds for their potential as therapies. Discussion focused on several safety, regulatory, cell-source and production issues that will need to be addressed before this approach is ready for clinical trials in people with MS.
Promoting Clinical Trials of Cell Therapy:
Controlled clinical trials by investigators were deemed an optimal way to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS.
A past roadblock has been that clinicians often use different treatment protocols, making it hard to compare results. Participants heard potential solutions to standardizing protocols and creating networks for centralizing data collection and analysis.
There are outstanding questions about how to track transplanted cells within the body, how to determine if cell therapy is working, and ethical challenges for cell-based therapies, including the issue of patient-funded studies and the problems of unregulated stem cell clinics
Breakout sessions focused on developing consensus about future clinical trial designs for each cell type, including the appropriate study populations for each cell type, the role of cell therapy in relation to the use of approved disease-modifying therapies
, dosing, route and frequency of delivery, and determining appropriate efficacy outcomes and safety monitoring steps.
: Conference organizers are already at work summarizing ideas and findings to publish a review of the field, which will help drive researchers and funding organizations toward activities that are most likely to provide answers around the best approaches for cell-based therapies for improving treatment options for people with MS. The National MS Society and other conference sponsors will continue to update constituents on progress related to this important work.
about stem cells and MS