title: Targets for therapy in sarcomeric cardiomyopathies.
abstract: To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics.
authors: Department of Medicine and Cellular and Molecular Medicine, University of Arizona, 1656 East Mabel Street, MRB 312, Tucson, AZ 85724-5217, USA jtardiff@email.arizona.edu j.vandervelden@vumc.nl.
authors: Jil C
authors: JC
authors: Tardiff
authors: Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors: Lucie
authors: L
authors: Carrier
authors: Department of Pharmacology, University of California, Davis, CA, USA.
authors: Donald M
authors: DM
authors: Bers
authors: Center of Molecular Medicine and Applied Biophysics (CIMMBA), University of Florence, Florence, Italy.
authors: Corrado
authors: C
authors: Poggesi
authors: Center of Molecular Medicine and Applied Biophysics (CIMMBA), University of Florence, Florence, Italy.
authors: Cecilia
authors: C
authors: Ferrantini
authors: Center of Molecular Medicine and Applied Biophysics (CIMMBA), University of Florence, Florence, Italy.
authors: Raffaele
authors: R
authors: Coppini
authors: Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum, Regensburg, Germany.
authors: Lars S
authors: LS
authors: Maier
authors: Experimental Therapeutics and Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors: Houman
authors: H
authors: Ashrafian
authors: Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Sabine
authors: S
authors: Huke
authors: Department of Physiology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands ICIN-Netherlands Heart Institute, Utrecht, the Netherlands jtardiff@email.arizona.edu j.vandervelden@vumc.nl.
authors: Jolanda
authors: J
authors: van der Velden
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D012518:Sarcomeres / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D005819:Genetic Markers
keywords: Dilated cardiomyopathy; Energetics and microvasculature; Gene therapy; Hypertrophic cardiomyopathy; Ion channels
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