Advances in the immune pathogenesis and treatment of multiple sclerosis.
Multiple sclerosis (MS) is a disorder of the central nervous system (CNS). It is characterized by episodic and progressive neurological dysfunction resulting from inflammatory and autoimmune reactions, myelin loss, conduction block, oligodendrocyte pathology, gliosis, and axonal loss in CNS. Recent years have witnessed advances in better understanding the immune pathogenesis of MS, prompted by animal models, human pathological observations and MRI studies. There have been significant changes in the therapeutic regimens in MS, with an emphasis on preventative treatment of an ongoing disease process. Agents in use and in the research pipeline have mechanisms that act on various anti-inflammatory and immunomodulatory properties, including blocking leukocyte migration into CNS and targeting chemoattraction. In addition, recent studies on the neurodegenerative components of MS have directed therapeutic trials to neuroprotection and neurorestoration. In this paper, we summarize the current understanding of the mechanisms of approved pharmacological agents and review the putative mechanisms and status of some important agents in clinical phase two or three trials in MS.
Huang
DeRen
D
Center for Multiple Sclerosis, Neurology and Neuroscience Associates, Inc., Akron, OH 44302, USA. dhuang@nnadoc.com
Rae-Grant
Alexander
A
D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology / Q000627:therapeutic use; D002448:Cell Adhesion; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007273:Injections, Intramuscular; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents