title: Gene Therapy in Heart Failure.
abstract: Heart failure is a significant burden to the global healthcare system and represents an underserved market for new pharmacologic strategies, especially therapies which can address root cause myocyte dysfunction. Modern drugs, surgeries, and state-of-the-art interventions are costly and do not improve survival outcome measures. Gene therapy is an attractive strategy, whereby selected gene targets and their associated regulatory mechanisms can be permanently managed therapeutically in a single treatment. This in theory could be sustainable for the patient's life. Despite the promise, however, gene therapy has numerous challenges that must be addressed together as a treatment plan comprising these key elements: myocyte physiologic target validation, gene target manipulation strategy, vector selection for the correct level of manipulation, and carefully utilizing an efficient delivery route that can be implemented in the clinic to efficiently transfer the therapy within safety limits. This chapter summarizes the key developments in cardiac gene therapy from the perspective of understanding each of these components of the treatment plan. The latest pharmacologic gene targets, gene therapy vectors, delivery routes, and strategies are reviewed.
authors: Icahn School of Medicine at Mount Sinai, Cardiovascular Research Center, New York, NY, USA. anthony.fargnoli@mssm.edu.
authors: Anthony S
authors: AS
authors: Fargnoli
authors: Icahn School of Medicine at Mount Sinai, Cardiovascular Research Center, New York, NY, USA.
authors: Michael G
authors: MG
authors: Katz
authors: Icahn School of Medicine at Mount Sinai, Cardiovascular Research Center, New York, NY, USA.
authors: Charles R
authors: CR
authors: Bridges
authors: Icahn School of Medicine at Mount Sinai, Cardiovascular Research Center, New York, NY, USA.
authors: Roger J
authors: RJ
authors: Hajjar
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D056966:Excitation Contraction Coupling / Q000235:genetics; D005355:Fibrosis / Q000235:genetics; D055879:Gene Knock-In Techniques; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D009206:Myocardium; D009210:Myofibrils / Q000235:genetics; D011943:Receptors, Adrenergic, beta; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases
keywords: Gene therapy; Gene therapy vectors; Heart failure; Molecular targets; Routes of gene delivery