Potential MS Therapy Shows Promising Efficacy, Avoids Immune Suppression
Researchers from the Thomas Jefferson University have designed an antigen-specific therapy for the autoimmune disease multiple sclerosis (MS) using oligodendrocyte-derived extracellular vesicles. The new treatment, reported in a new edition of Science Translational Medicine, doesn’t suppress the immune system like traditional therapies, representing a much-needed alternative to conventional approaches to MS, most of which are associated with serious side effects.
In MS, the immune system attacks the myelin sheath, an insulating layer that wraps around nerves in the brain and spinal cord. Currently, scientists do not have a thorough understanding of which myelin antigens trigger the immune system attack in MS. Additionally, there is a current lack of consensus on the extent of the responsibility of different antigens in terms of disease onset and progression. Finally, the research is unclear as to whether or not immune-targeted antigens evolve in patients with MS.
“There are many possible immune-activating antigens in the myelin sheath, but the biggest hurdle is that we don’t know which component of myelin is triggering the immune response in MS patients,” added corresponding study author Abdolmohamad Rostami, M.D., Ph.D., Professor and Chairman of the Department of Neurology at Sidney Kimmel Medical College-Thomas Jefferson University and Vickie and Jack Farber Institute for Neuroscience-Jefferson Health, in a previously published interview with Genetic Engineering & Biotechnology News.
In their Science Translational Medicine paper, the investigators report that most scientists believe the pathogenesis of MS is driven by autoimmunity against oligodendrocyte–produced myelin antigens.
The researchers who developed the new oligodendrocyte-derived extracellular vesicle therapy note that traditional MS drugs combat the inflammatory response associated with the disease by suppressing the immune system. While this may help reduce the immune system’s ability to attack the myelin sheath that covers the central nervous system, the investigators say this can also lead to serious side effects. Adverse effects associated with immune suppression include higher risks of infection and, in some instances, cancer.
The new therapeutic approach relied on tiny extracellular vesicles released by oligodendrocytes that generate the myelin sheath. Extracellular vesicles are capable of being harvested from cultured oligodendrocytes, and many of them contain nearly all of the relevant myeline antigens. Thus, the therapeutic strategy contains multiple myeline antigens and, in theory, may increase the chance that the extracellular vesicles stop the autoimmune attack on the myelin sheath.
In in vivo mouse experiments, intravenous injection of the therapy prevented the onset of MS symptoms (e.g., reduced mobility and paralysis) when injected before disease development. Injected after disease onset, the extracellular vesicles reduced disease severity in three mouse models representing early and late stages of the disease. Animals even regained their ability to walk again following treatment injection.
“Given that oligodendrocyte-derived extracellular vesicles contain most, or possibly all, relevant myelin antigens, they have the potential to induce antigen-specific tolerance and suppress disease driven by an immune response against myelin antigens,” the investigators wrote in their paper. “Hence, the use of oligodendrocyte-derived extracellular vesicles would sidestep the need to identify relevant myelin Ag(s) in each patient, raising the possibility that oligodendrocyte-derived extracellular vesicles may be a universally applicable antigen-specific MS therapy.”
The findings of the mouse model also indicate the therapy leaves the immune system intact, suggesting it does not weaken the overall immune system like other MS treatments.
In their research, the investigators also isolated extracellular vesicles from human-derived oligodendrocytes, all of which contained multiple myelin antigens. Based on this finding, the researchers theorize the results in the animal models could generalize to human patients. The investigators are currently working toward a patent for the intravenous extracellular vesicle approach.