University of Cincinnati

University of Colorado

Other

Genaissance Pharmaceuticals, Inc.

Stephen Bryant Liggett

Kersten M Small

Michael R Bristow

Krishnan Nandabalan

Gerald W Dorn, Ii

Richard S Judson

J Claiborne Stephens

Catherine B Stack

Connie M Drysdale

Lynne Elizabeth Wagoner

The present invention concerns the use of methods for evaluating bucindolol treatment for a patient, particularly one with heart failure. It concerns methods for determining whether to administer or prescribe bucindolol to a patient based on whether the patient is homozygous for the Arg 389 polymorphism in the &#x3b2;1-adrenergic receptor (AR).

Methods for treatment with bucindolol based on genetic targeting

The present invention is directed to compositions and methods relating to a G-protein coupled receptor kinase-5 polymorphism. The methods include, for example: detecting enhanced desensitization of the beta adrenergic receptor signaling pathway in an individual, assessing partial protection against heart failure progression in an individual, and assessing an individual's response to beta-blocker therapy. The compositions include polynucleotides or fragments thereof of a nucleotide sequence encoding for a G-protein receptor kinase-5 molecule with a thymine at amino acid position 122 and oligonucleotide primers that hybridize thereto.

G-protein coupled receptor kinase-5 polymorphism

A pharmaceutical composition comprising an expression product of a Type Nine adenylyl cyclase gene polymorphism, along with a suitable physiological carrier, are provided. In addition, methods related to treating patients having asthma or a reversible bronchial obstruction, kits for determining the responsiveness of an individual to treatment regimens, and assays for screening pharmaceutical for efficacy in treatment are also provided.

Pharmaceutical and therapeutic applications relating to a type 9 adenylyl cyclase Polymorphism in asthma and reversible bronchial obstruction

Methods for cardiovascular disease assessment in an individual comprise detecting the presence or absence of a fragment encoding a polymorphic alpha-2C (&#x3b1;DEL322-325) adrenergic receptor in a sample from an individual; and detecting the presence or absence of a fragment encoding a polymorphic beta-1 adrenergic receptor (&#x3b2;Arg389) in a sample from the individual. Methods for delaying development of cardiovascular disease in an individual, methods for delaying progression or early death associated with cardiovascular disease in an individual, methods of genetic counseling for cardiovascular disease in an individual are also provided.

Heart failure assessment based on alpha-2C adrenergic receptor polymorphisms

The present invention includes polymorphisms in nucleic acids encoding the alpha-2B, alpha-2A, and alpha-2C adrenergic receptor and expressed alpha-2B, alpha-2A and alpha-2C adrenergic receptor molecule. The invention also pertains to methods and molecules for detecting such polymorphisms. The invention further pertains to the use of such molecules and methods in the diagnosis, prognosis, and treatment of diseases such as cardiovascular and central nervous system disease.

Alpha-2 adrenergic receptor polymorphisms

Methods and compositions for the detection, diagnosis, and prevention of cardiac conditions are provided. Polymorphisms of &#x3b2;-adrenergic receptor are provided. The Gly389 &#x3b2;-adrenergic receptor variants are not as responsive to treatment &#x3b2; blockers such as carvedilol, metoprolol or bisoprol. Thus, genotyping &#x3b2;-adrenergic receptor polymorphisms is useful for predicting relative responsiveness to treatment with beta blockers. The Gly389 polymorphism also may be used, alone or in conjunction with other adrenergic receptor polymorphisms, to predict relative risk of developing cardiovascular diseases such as heart failure or to predict relative survival rate in patients with heart failure or other cardiovascular diseases. Also provided are transgenic mice and transgenic cells expressing the &#x3b2;-adrenergic receptor polymorphisms, and their use in identifying therapeutic agents.

Methods for predicting relative efficacy of a beta blocker therapy based on a B1-adrenergic receptor polymorphism

The present invention includes polymorphisms in nucleic acids encoding the alpha-2B adrenergic receptor and expressed alpha-2B adrenergic receptor molecule. The invention also pertains to methods and molecules for detecting such polymorphisms. The invention further pertains to the use of such molecules and methods in the diagnosis, prognosis, and treatment of diseases such as cardiovascular and central nervous system diseases.

Alpha-2B-adrenergic receptor polymorphisms

The present invention includes polymorphisms in nucleic acids encoding the alpha-2A adrenergic receptor and expressed alpha-2A adrenergic receptor molecule. The invention also pertains to methods and molecules for detecting such polymorphisms and transgenic animals expressing alpha-2A adrenergic receptor molecules. The invention further pertains to the use of such molecules and methods in the diagnosis, prognosis, and treatment of diseases such as cardiovascular and central nervous system diseases.

Alpha-2A-adrenergic receptor polymorphisms

A novel polymorphic site in the 5' leader cistron of the &#x3b2;-adrenergic receptor (&#x3b2;AR) gene is disclosed. The polymorphisms present at this site result in different levels of inhibition of translation of &#x3b2;AR mRNA. Compositions and methods for genotyping this polymorphic site as disclosed. In addition, methods for using this genotype information are disclosed, including predicting genetic predisposition to a disease modified by &#x3b2;AR expression and predicting a patient's bronchodilating response to &#x3b2;-agonists.

Variation in drug response related to polymorphisms in the &#x3b2;2-adrenergic receptor

A method for predicting an individual's response to the &bgr;-agonists salmeterol, albuterol, metaproterenol, terbutaline and formoterol is disclosed. Individuals expressing the Ile164 &bgr; AR variant are likely to exhibit a reduced response as compared to individuals expressing the Thr164 &bgr; AR variant. The method is useful for making treatment decisions for patients suffering from asthma and chronic obstructive pulmonary diseases.

Variation in drug response related to polymorphisms in &bgr;2-adrenergic receptor

Genotypes and haplotypes for thirteen polymorphic sites in the &bgr; -adrenergic receptor (&bgr; AR) gene are disclosed. Compositions and methods for predicting genetic predisposition to disease associated with polymorphic sites in the (&bgr; AR) gene, as well as for predicting response to &bgr;-agonists, are also disclosed.

Growing community of inventors

Cincinnati, OH, United States of America

Stephen Bryant Liggett