title: Emerging pharmacologic targets and treatments for myocarditis.
abstract: Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alteration of the immune response and antiviral treatments; however, success has been limited. Since the myocarditis treatment trials in the 1990s there has been an improved understanding of disease progression and new facets of the immune response have been discovered. This new information provides fresh opportunities to develop therapeutics to treat myocarditis. This review analyzes previous pharmacologic approaches including immunosuppression, high dose intravenous immunoglobulin treatment, immunoadsorption and antiviral treatments, and looks forward toward recently identified immune factors that can be exploited as targets for new treatments. Such strategies include bolstering beneficial regulatory T cells or mitigating the detrimental Th17 T cells which can drive autoimmunity in the heart. The surging interest of the application of humanized monoclonal antibodies makes targeting deleterious arms of the immune response like Th17 cells a tangible goal in the near future. Promising constituents of herbal remedies have also been identified that may hold potential as new pharmacological treatments for myocarditis, however, significant work remains to elucidate the pharmacokinetics and side-effects of these compounds. Finally, advances in our understanding of the function of Matrix Metalloproteinases yield another target for altering disease progression given their role in the development of fibrosis during Dilated Cardiomyopathy. In bringing to light the various new targets and treatments available since the last myocarditis treatment trials, the aim of this review is to explore the new treatments that are possible in new myocarditis treatment trials.
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Jensen
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: marchant@ualberta.ca.
authors.forename: David J
authors.initials: DJ
authors.lastname: Marchant
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy; D015507:Drugs, Investigational / Q000627:therapeutic use; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D009205:Myocarditis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000469:parasitology; D028321:Plant Preparations / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001323:Autoantibodies; D015507:Drugs, Investigational; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D061965:Matrix Metalloproteinase Inhibitors; D028321:Plant Preparations; D020782:Matrix Metalloproteinases