Relapses Prevented in Multiple Sclerosis Mouse Model
Researchers at the University of Heidelberg, Germany, recently showed that peripheral blood cells loaded with a drug that resembles the myelin protein are able to inhibit harmful immune responses and prevent relapses in a mouse model of relapsing-remitting multiple sclerosis (MS).
The findings were described in the study “Autoantigen-specific immunosuppression with tolerogenic peripheral blood cells prevents relapses in a mouse model of relapsing-remitting multiple sclerosis,” and published in the Journal of Translational Medicine.
MS is a chronic inflammatory disease, characterized by the degradation of the myelin sheaths surrounding the nerve cells. Since the immune system is known to play a crucial role in this process, there have been many attempts to control the disease’s path of development by inhibiting the immune response. However, the approaches are commonly unspecific, and lead to side effects due to a generalized immunosuppression.
In previous studies, the authors had managed to prevent the experimental autoimmune encephalitis (EAE) mouse model for MS, by previously injecting the animals with dendritic cells (DCs) loaded with myelin basic protein (MBP), a brain derived autoantigen. Treated with a chemotherapeutic agent – mitomycin (MMC) -, showed that autoantigen-loaded, MMC-treated DCs could be used as a protective vaccine.
Recently, the research team, led by Peter Terness, addressed whether the approach could be used as therapy against an ongoing disease. To avoid the risk of exacerbating the disease with autoantigens, the MBP was switched by a random copolymer of amino acids, called “glatiramer acetate” (Copaxone) which is a drug approved for the treatment of relapsing-remitting MS that highly mimicks MBP.
Because never before exposed DCs are stimulatory cells, even after being rendered suppressive by MMC treatment, they regain stimulatory capacity which led investigators to address if DCs could be replaced by peripheral blood cells (PBMC), which are less immunogenic and much easier to prepare.
Results revealed that injection of PBMCs loaded with Copaxone and induced with MMC was able to inhibit the harmful autoreactive immune response and prevent further relapses in mice models of MS – possibly by the increased infiltration of regulatory T cells that secrete specific cytokine molecules known to suppress other immune cells. Importantly, the general immune responses were not affected.
The study concluded: “Donor MIC [MMC-induced] cell therapy is currently being implemented in living donor kidney transplantation. The findings of the present study, although not clarifying all mechanistic questions, constitute a sound basis for a clinical phase I study with MICCop cells in patients with MS.”