December 4, 2020
An international research team has published results that open new possibilities for developing ways to repair nerve-insulating myelin in people with multiple sclerosis. Along with a companion study previously published, the team’s research addresses an important question in MS: why do the brain’s normal repair mechanisms eventually fail to repair damage to myelin in the brain and spinal cord? Nerve fibers (axons) stripped of their myelin are less likely to survive immune-system assaults that are the hallmark of MS.
Background: Myelin is a coating that improves nerve conduction and is damaged during the course of multiple sclerosis. The brain has spare stem cells, called oligodendrocyte precursor cells (OPCs), that are capable of moving to damaged areas, becoming mature myelin making cells (oligodendrocytes), and producing and wrapping new myelin around axons. However, at some point during the MS disease process, myelin repair stalls. It is not clear whether repair stalls because of some fault in the OPCs themselves, or some fault in the environment of MS lesions, such as toxic immune activity.
The Study: A team headed by Dr. Anne Baron-Van Evercooren (INSERM, Paris), in collaboration with Dr. Tanja Kuhlmann (University Hospital Münster), Dr. Jack Antel (McGill University, Montreal), and Dr. Gianvito Martino (San Raffaele Hospital and Vita San Raffaele University, Milan), addressed this question by testing the ability of OPCs to form myelin in mice with an inborn myelin deficiency. In these mice, there was no interference by immune activity.
The team took skin cells from three people with MS and three people without MS, including a healthy twin of a person with MS. They used what is becoming standard technology to reverse-program the skin cells to become stem cells -- “induced pluripotent stem cells” (iPSCs), which were further coaxed to become young OPCs. These “induced” OPCs were then injected into the nervous systems of the mice, and the cells’ movements and activities were traced.
Findings: The researchers found no difference in the behavior of OPCs derived from MS skin cells and those from healthy individuals. The cells went through normal stages of growth, maturity, and specialization to become myelin-making oligodendrocytes. They interacted functionally with the mouse’s other brain cells (specifically, oligodendrocytes and astrocytes). They formed myelin around axons, networked with other oligodendrocytes, and improved the efficiency of nerve conduction.
This study confirms recent evidence from Dr. Kuhlmann’s lab (Acta Neuropathologica (2020) 140:715–736), obtained in collaboration with the same teams involved in the present study, indicating that in lab dishes the OPCs derived from MS skin cells behaved similarly to those from healthy individuals on a proteomic level – meaning the full complement of proteins present and active (expressed) in the cells were very similar.
Meaning and Potential Impacts: These results imply that MS does not change the inherent capacity of oligodendrocytes to repair myelin, and that the fault is more likely the brain environment. In addition to immune factors, other factors that have been implicated in myelin repair failure in MS include aging and axonal damage.
Taken together, these studies add important evidence about the potential for myelin repair in MS, and also suggest that iPSCs derived from skin or other cells of people with MS may be a viable source of cells for myelin repair therapy in the future. Research using iPSCs is still in its infancy as studies proceed to determine whether any types of stem cells can reverse MS damage and restore function.
Funding: Dr. Baron-Van Evercooren is a co-investigator on the Collaborative Research Network (BRAVEinMS) led by Dr. Martino. The Network, supported by the International Progressive MS Alliance, also collaborates with the research groups led by Dr. Kuhlmann and Dr. Antel, and others. This research was also funded by the National MS Society (USA, the Italian Multiple Sclerosis Foundation and others.
“Multiple sclerosis iPS-derived oligodendroglia conserve their properties to functionally interact with axons and glia in vivo” (by Sabah Mozafari, Laura Starost, Blandine Manot-Saillet, Beatriz Garcia-Diaz,Yu Kang T. Xu, Delphine Roussel, Marion J. F. Levy, Linda Ottoboni, Kee-Pyo Kim, Hans R. Schöler, Timothy E. Kennedy, Jack P. Antel, Gianvito Martino, Maria Cecilia Angulo, Tanja Kuhlmann, Anne Baron-Van Evercooren) was published in Science Advances on December 4, 2020.
About the International Progressiv MS Alliance
The Alliance exists to accelerate the development of effective treatments for people with progressive forms of multiple sclerosis to improve quality of life worldwide. It is an unprecedented global collaboration of MS organisations, researchers, health 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 ─ rallying the global community to find solutions. Our promise is more than hope, it is progress.
The Italian MS Society with its Foundation is a member of the International Progressive MS Alliance and supported this study.