Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy

Abstract

Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.

Keywords: autoimmunity; cell-based therapy; multiple sclerosis; neuroprotection; tolerance.

Fig. 1

Multiple sclerosis pathogenesis in both relapsing and progressive disease. Scheme representing the major cells and molecules that play a role in the two different stages of MS. The dashed line allows comparison of the differences between relapsing and progressive MS. Arrows indicate release, while inhibitors indicate inhibition. The black arrowhead on a dotted line indicates transmigration. CSF cerebrospinal fluid, DC dendritic cells, GM-CSF granulocyte-macrophage colony-stimulating factor, IFN interferon, IL interleukin, ILCs innate lymphoid cells, MAIT cells mucosal-associated invariant T cells, MS multiple sclerosis, RNS reactive nitrogen species, ROS reactive oxygen species, SAS subarachnoid space, Th T helper

Fig. 2

Proposed mechanisms of action of approved treatments for multiple sclerosis and cell-based therapies. Representation of the mechanisms of action of current treatments (black boxes) and cell-based therapies (gray boxes). Arrows indicate induction, while inhibition symbols indicate inhibition. Breg regulatory B cells, CNS central nervous system, DC dendritic cells, MAIT cell mucosal-associated invariant T cells, NK natural killer cells, Th T helper, Treg regulatory T cells