Wisconsin Alumni Research Foundation

Xenon Pharmaceuticals Inc.

Harvard College

The University of British Columbia

Xenon Genetics Inc.

Alan D Attie

Mark Gray-Keller

Mark Patrick Keller

Michael R Hayden

James M Ntambi

Makoto Miyazaki

Alison J Brownlie

Ronald Thaddeus Raines

Samuel Helmer Gellman

Alan Saghatelian

Lisa M Johnson

Mary E Rabaglia

Daniel G Gretch

Stephen L Sturley

Mark Eric Cook

Weiping Tang

Simon N Pimstone

Angela R Brooks-Wilson

Jan Peter Van Pijkeren

Jee-Hwan Oh

Ka Yang

Gabrielle N Winston-McPherson

Donald L Gillian-Daniel

Paul W Bates

Samuel T Nadler

Michelle Kimple

Haibo Xie

Nancy E Beckage

Mark P Gray-Keller

Described are benzoimidazole indolyl methane compounds, pharmaceutical compositions containing them, and use of the compounds to inhibit PCSK9-mediated ailments. The compounds have the structure: 

Benzoimidazole indolyl methanes and methods of using them to inhibit PCKS9 and PCKS9-mediated ailments

Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one &#x3b1;-amino acid found in the native GLP-1 is replaced with a &#x3b2;-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Alpha/beta-polypeptide analogs of glucagon-like peptide 1

Methods and microorganisms for systemically introducing a polypeptide in the bloodstream of a subject. The methods of the invention include administering into the gastrointestinal tract of a subject a bacterium configured to express and produce and release the polypeptide. The bacterium is administered in an amount effective to introduce the polypeptide in the bloodstream of the subject, preferably in a detectable amount. The microorganisms of the invention include lactic acid bacteria, such as, that comprise a recombinant gene configured to express a polypeptide to be systemically introduced.

Methods for systemically delivering polypeptides and microorganisms therefor

Alpha/beta-polypeptide analogs of glucagon-like peptide-1

Provided herein are methods for increasing insulin secretion from beta cells. Also provide herein are methods comprising administering to a subject in need of increased insulin secretion a composition comprising a compound that directly or indirectly activates adenylate cyclase and an E prostanoid 3 (EP3) receptor antagonist that attenuates G alpha-i-subfamily (GSIS)-mediated adenylate cyclase inhibition.

E-prostanoid receptor, Ptger3, as a novel anti-diabetic therapeutic target

The present invention relates to a recognition that an analog of &#x3b1;KG can increase glucose-induced insulin secretion in vitro and in vivo in animals, particularly in mammals, and more particularly in humans and in rodents. By employing the methods of the invention, insulin secretion can be increased.

Potentiators of insulin secretion

The use of screening assays based on the role of human stearoyl-CoA desaturase-1 ('hSCD1') in human diseases, disorders or conditions relating to serum levels of triglyceride, VLDL, HDL, LDL, total cholesterol, or production of secretions from mucous membranes, monounsaturated fatty acids, wax esters, and the like, is disclosed. Also disclosed are conventions useful in the prevention and/or treatment of such diseases.

Methods and compositions using stearoyl-CoA desaturase to identify triglyceride reducing therapeutic agents

It has been discovered that the low density lipoprotein receptor (LDLR) degrades the lipoprotein apoB. Based on this observation, an artificial fusion protein has been designed containing an LDL receptor domain attached to a localization domain which causes retention of the fusion protein inside of a cell. The fusion protein is preferably retained in the endoplasmic reticulum of the cell, where the LDLR can degrade apoB. Data shows that the technique is effective in a mammal to reduce serum LDL cholesterol levels.

Inhibition of lipoprotein secretion

A gene expression pattern analysis has identified genes the expression patterns of which are different in adipose cells of individuals who have Type 2 Diabetes Mellitus from the cells of individuals who do not have the disease. This information provides a mechanism for the genetic diagnosis of the disease.

Methods of diagnosing susceptibility to obesity

Methods and compounds are disclosed for lowering serum LDL levels or serum cholesterol levels, or for reducing the transport of cholesterol from the gut to the blood or the lymph, based on the observation that a gene known as ABC1 is necessary in order for cholesterol to be transported from the intestinal lumen into the bloodstream. A mutant chicken phenotype, known as the WHAM chicken, characterized by low levels of serum LDL and reduced transport of cholesterol, facilitated the discovery of this function of the ABC1 gene. Techniques which act to inhibit ABC1 activity in the cells of the intestinal wall will result in lower serum cholesterol.

Cholesterol transport gene

A truncation of the human LDL receptor gene has been created which can be expressed in a heterologous host to produce a soluble fragment to the receptor protein. The gene can be expressed in insect cells in culture to produce a protein fragment which is not only water soluble but which also retains affinity for binding to LDL. The truncation is a truncation of the carboxyl terminus of the native LDL receptor gene which results in a 354 amino acid protein fragment designated LDL-R.sup.354.

Soluble LDL receptor and gene

Growing community of inventors

Madison, WI, United States of America

Alan D Attie