References in periodicals archive ?
Patent and Trademark Office (USPTO) has issued a patent on methods for determining whether to administer or prescribe bucindolol to a patient based on whether the patient has a specific genotype - homozygous for the arginine 389 polymorphism in the beta-1 adrenergic receptor.
This genetic substudy, published recently in the Proceedings of the National Academy of Sciences, shows that a common genetic variation in the beta-1 adrenergic receptor may help doctors identify heart failure patients who may benefit most from bucindolol.
The new test identifies common genetic variations of the alpha-2c and the beta-1 adrenergic receptors that regulate the human heart.
In this study, Gencaro appeared to produce enhanced clinical outcomes in the 47% of patients who were homozygous for the amino acid position 389 arginine polymorphism of the beta-1 adrenergic receptor, a variant with higher functional activity and higher affinity for norepinephrine, which the Company believes is the most favorable genotype for a positive response to Gencaro.
In the placebo-controlled study, the researchers found a 38 percent reduction in the death rate and a 36 percent reduction in hospitalizations in patients who took bucindolol and also had two copies of a genetic variant in the beta-1 adrenergic receptor called 389 arginine (Arg-389).
Results from the GRAHF study on two gene variations in aldosterone synthase and beta-1 adrenergic receptor were presented in Atlanta at the 55th Annual Scientific Session of the American College of Cardiology.
Four separate posters were presented including Phase III clinical results of nebivolol in the treatment of hypertension and the results of pre-clinical studies on the compound's antioxidant properties, its ability to stimulate nitric oxide (NO) release from endothelial cells in White and African American donors, and its high degree of beta-1 adrenergic receptor selectivity, as demonstrated in laboratory studies.
In 2008, the StaR technology was used successfully to elucidate the three-dimensional atomic resolution structure of the beta-1 adrenergic receptor, which is the site of action of beta blockers.
The investment was triggered by the excellent progress made both by HTL's in-house team and by its founding scientists at the MRC Laboratory of Molecular Biology, Cambridge, who have recently solved the structure of the beta-1 adrenergic receptor based on their novel GPCR-stabilisation methodology.
The Bristow/Aleong editorial comments that the data from BEST appear to be different from the data for the drugs evaluated in the Rienstra study, because retrospective analyses of the data from BEST appear to show evidence of efficacy for Gencaro in HFREF patients with AF, and enhanced efficacy for those HFREF patients with AF who possess a common genetic variant in the cardiac beta-1 adrenergic receptor (AR), the primary drug target of beta-blockers for cardiovascular indications.
In addition, results were reported from the large (1,040 patient) DNA substudy of BEST, a hypothesis-driven, prospectively-designed study initiated during the trial that examined the effects of bucindolol in beta-1 adrenergic receptor gene variants (beta-1 389 Arg/Arg and Gly carriers).
As previously reported at the American Heart Association's Scientific Sessions 2011, Gencaro reduced the risk of developing AF by 74% in the genetic subgroup that was homozygous for the 389 arginine version of the beta-1 adrenergic receptor, which has high affinity for norepinephrine.