Gene therapy is emerging as a potential treatment option in patients suffering from a wide spectrum of cardiovascular diseases including coronary artery disease, peripheral vascular disease, vein graft failure and in‐stent restenosis. Thus far preclinical studies have shown promise for a wide variety of genes, in particular the delivery of genes encoding growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) to treat ischaemic vascular disease both peripherally and in coronary artery disease. VEGF as well as other genes such as TIMPs have been used to target the development of neointimal hyperplasia to successfully prevent vein graft failure and in‐stent restenosis in animal models. Subsequent phase I trials to examine safety of these therapies have been successful with low levels of serious adverse effects, and albeit in the absence of a placebo group some suggestion of efficacy. Phase 2 studies, which have incorporated a placebo group, have not confirmed this early promise of efficacy. In the next generation of clinical gene therapy trials for cardiovascular disease, many parameters will need to be adjusted in the search for an effective therapy, including the identification of a suitable vector, appropriate gene or genes and an effective vector delivery system for a specific disease target. Here we review the current status of cardiovascular gene therapy and the potential for this approach to become a viable treatment option.
British Journal of Pharmacology (2007) 152, 175–188; doi:
BackgroundData are limited about the burden of respiratory syncytial virus (RSV)-related hospitalizations in older adults and those with COPD or CHF.MethodsWe conducted prospective surveillance at two hospitals from October 2018 to March 2019 for adults ≥50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region in Atlanta, Georgia. Asymptomatic adults ≥50 years of age were enrolled as controls. Nasopharyngeal and oropharyngeal swabs were tested for RSV and influenza (Flu) using BioFire® FilmArray® Respiratory Viral Panel (RVP) and acute/convalescent serology was obtained for RSV antibodies detection by enzyme immunoassay against RSV lysate. Standard of care results were included for enrollees. We compare the number of RSV+, Flu+ and RSV−/Flu− cases along with demographic features and outcomes.ResultsWe screened 12,453 patients to identify 1,515 eligible adults of which 617 (41%) were enrolled. The most common reasons for failing to enroll were refusal (676, 75%) and inability to obtain informed consent (221, 25%). Of the 617, 36 (6%) were RSV+ and 41 (7%) were Flu+. RSV was detected in 1/126 (0.8%) and Flu in 0/126 healthy controls. RSV+ occurred earlier in surveillance and peaked at a higher frequency (figure). Clinical characteristics and outcomes are in the table. In a convenience sample, a four-fold rise in RSV antibody titer was detected among 8/15 RSV+, 0/42 RSV−/Flu−, and 0/42 healthy controls.ConclusionThe burden and outcomes for RSV are similar to Flu in adults admitted to the hospital with ARI, CHF, or COPD. A vaccine for RSV would be beneficial.
DisclosuresNadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant.
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