RESUMEN
Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist concerning the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without preexisting cardiovascular disease. In September 2017, the National Heart, Lung, and Blood Institute convened a Working Group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease. The Working Group reviewed and discussed the roles of normal thyroid physiology, the consequences of thyroid dysfunction, and the effects of therapy in 3 cardiovascular areas: cardiac electrophysiology and arrhythmias, the vasculature and atherosclerosis, and the myocardium and heart failure. This report describes the current state of the field, outlines barriers and challenges to progress, and proposes research opportunities to advance the field, including strategies for leveraging novel approaches using omics and big data. The Working Group recommended research in 3 broad areas: (1) investigation into the fundamental biology relating thyroid dysfunction to the development of cardiovascular disease and into the identification of novel biomarkers of thyroid hormone action in cardiovascular tissues; (2) studies that define subgroups of patients with thyroid dysfunction amenable to specific preventive strategies and interventional therapies related to cardiovascular disease; and (3) clinical trials focused on improvement in cardiovascular performance and cardiovascular outcomes through treatment with thyroid hormone or thyromimetic drugs.
RESUMEN
Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist concerning the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without preexisting cardiovascular disease. In September 2017, The National Heart, Lung, and Blood Institute convened a Working Group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease. The Working Group reviewed and discussed the roles of normal thyroid physiology, the consequences of thyroid dysfunction, and the effects of therapy in three cardiovascular areas: cardiac electrophysiology and arrhythmias, the vasculature and atherosclerosis, and the myocardium and heart failure. This report describes the current state of the field, outlines barriers and challenges to progress, and proposes research opportunities to advance the field, including strategies for leveraging novel approaches using omics and big data. The Working Group recommended research in three broad areas: 1) investigation into the fundamental biology relating thyroid dysfunction to the development of cardiovascular disease and into the identification of novel biomarkers of thyroid hormone action in cardiovascular tissues; 2) studies that define subgroups of patients with thyroid dysfunction amenable to specific preventive strategies and interventional therapies related to cardiovascular disease; and 3) clinical trials focused on improvement in cardiovascular performance and cardiovascular outcomes through treatment with thyroid hormone or thyromimetic drugs.
Asunto(s)
Enfermedades Cardiovasculares/terapia , Investigación , Enfermedades de la Tiroides/terapia , Enfermedades Cardiovasculares/prevención & control , Humanos , Enfermedades de la Tiroides/prevención & controlRESUMEN
Over a 10-year period, the Gene Therapy Resource Program (GTRP) of the National Heart Lung and Blood Institute has provided a set of core services to investigators to facilitate the clinical translation of gene therapy. These services have included a preclinical (research-grade) vector production core; current Good Manufacturing Practice clinical-grade vector cores for recombinant adeno-associated virus and lentivirus vectors; a pharmacology and toxicology core; and a coordinating center to manage program logistics and to provide regulatory and financial support to early-phase clinical trials. In addition, the GTRP has utilized a Steering Committee and a Scientific Review Board to guide overall progress and effectiveness and to evaluate individual proposals. These resources have been deployed to assist 82 investigators with 172 approved service proposals. These efforts have assisted in clinical trial implementation across a wide range of genetic, cardiac, pulmonary, and blood diseases. Program outcomes and potential future directions of the program are discussed.
Asunto(s)
Dependovirus/genética , Terapia Genética/tendencias , Lentivirus/genética , Investigación Biomédica Traslacional/tendencias , Aniversarios y Eventos Especiales , Vectores Genéticos , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Estados UnidosRESUMEN
With recent successes in gene therapy trials for hemophilia and retinal diseases, the promise and prospects for gene therapy are once again garnering significant attention. To build on this momentum, the National Institute of Neurological Disorders and Stroke and the Muscular Dystrophy Association jointly hosted a workshop in April 2014 on "Best Practices for Gene Therapy Programs," with a focus on neuromuscular disorders. Workshop participants included researchers from academia and industry as well as representatives from the regulatory, legal, and patient advocacy sectors to cover the gamut from preclinical optimization to intellectual property concerns and regulatory approval. The workshop focused on three key issues in the field: (1) establishing adequate scientific premise for clinical trials in gene therapy, (2) addressing regulatory process issues, and (3) intellectual property and commercialization issues as they relate to gene therapy. The outcomes from the discussions at this workshop are intended to provide guidance for researchers and funders in the gene therapy field.
Asunto(s)
Terapia Genética/métodos , Terapia Genética/normas , Enfermedades Neuromusculares/genética , Enfermedades Neuromusculares/terapia , Ensayos Clínicos como Asunto , Terapia Genética/legislación & jurisprudencia , Regulación Gubernamental , Humanos , Propiedad IntelectualRESUMEN
Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances.
Asunto(s)
Terapia Genética/ética , Animales , Educación Continua , Investigación Genética , Terapia Genética/economía , Terapia Genética/legislación & jurisprudencia , Vectores Genéticos , Humanos , National Institutes of Health (U.S.) , Investigación con Células Madre , Trasplante de Células Madre , Transducción Genética , Estados UnidosRESUMEN
Sonia I. Skarlatos, PhD (September 28, 1953-August 6, 2013), was the deputy director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). This article reviews her work in establishing, leading, or facilitating extramural translational research programs supported by the NHLBI, specifically focusing on her work as a consistent advocate for the advancement of gene and cell therapies.
Asunto(s)
Enfermedades Cardiovasculares/terapia , Terapia Genética , Programas de Gobierno , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Investigación con Células Madre , Investigación Biomédica Traslacional , Estados UnidosRESUMEN
Abstract Translational research is a lengthy, complex, and necessary endeavor in order to bring basic science discoveries to clinical fruition. The NIH offers several programs to support translational research including an important resource established specifically for gene therapy researchers-the National Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Resource Program (GTRP). This paper reviews the core components of the GTRP and describes how the GTRP provides researchers with resources that are critical to advancing investigational gene therapy products into clinical testing.