The J. David Gladstone Institutes

University of California

Duke University

The United States Government As Represented by the Department of Veterans Affairs

Karl H Weisgraber

Yadong Huang

Robert L Raffai

Warren J Strittmatter

Robert V Farese, Jr

Allen D Roses

Donald E Schmechel

Robert W Mahley

Qin Xu

Michel Goedert

Clare Peters-Libeu

Julie A Morrow

Thu Nga Bien-Ly

Li-Ming Dong

Ligong Chen

Ann M Saunders

The present disclosure provides synthetic antibodies specific for an epitope present on an apolipoprotein E polypeptide. The antibodies are useful in various treatment, diagnostic, and monitoring applications, which are also provided.

Antibody specific for apolipoprotein and methods of use thereof

The present invention provides compounds that inhibit apoE4 domain interaction; and compositions, including pharmaceutical compositions, comprising the compounds. The present invention provides methods of treating apoE4-related disorders. The methods generally involve administering to an individual in need thereof a therapeutically effective amount of an apoE4 domain interaction inhibitor.

ApoE4 domain interaction inhibitors and methods of use thereof

An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI) and an impaired ApoE expressor (Apoe) to generate a strain referred to as ApoeSRB1mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The ApoeSRB1mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge. The ability to rapidly and permanently lower blood cholesterol levels in these mice stops and may cause the regression of occlusive coronary atherosclerosis restoring blood flow to the heart, allowing the mice to survive from myocardial infarction and live with chronic heart failure.

Mouse model of chronic heart failure and coronary atherosclerosis regression

The present invention provides isolated apolipoprotein E (apoE) stable folding intermediates. The invention further provides methods for identifying compounds that alter the structure or level or activity of an apoE stable folding intermediate, as well as methods of inhibiting the formation or activity of stable folding intermediates of apoE. The invention further provides methods for reducing the level and/or activity of an apoE stable folding intermediate, and methods for treating disorders relating to apoE4 in a subject.

Apolipoprotein E stable folding intermediate and methods of use thereof

The invention provides gene-targeted non-human animals comprising a genetically modified apoE gene encodes a recombinant apoE polypeptide displaying domain interaction. The invention further provides cells isolated from the gene-targeted animals, which cells produce a recombinant apoE polypeptide displaying domain interaction. The invention further provides methods of identifying agents that reduce apoE4 domain interaction, and which are useful to treat apoE4-related neurological and cardiovascular disorders.

Gene-targeted animal model of apolipoprotein E4 domain interaction and uses thereof

A method of combatting Alzheimer's disease which comprises increasing the binding of the tau protein in nerve cells of that subject, and/or the binding of MAP2c protein in nerve cells of that subject, to either Apolipoprotein E or an Apolipoprotein E fragments capable of binding tau and/or MAP2c. In one embodiment, the method comprises administering the ApoE or ApoE fragment to the subject; in another embodiment, the method comprises administering to the subject a vector capable of entering nerve cells, which vector then upregulates the expression of an ApoE or an ApoE fragment capable of binding tau and/or MAP2c in nerve cells. Compositions useful for carrying out these methods are also disclosed.

Methods and compositions for binding tau and MAP2c proteins

Growing community of inventors

Walnut Creek, CA, United States of America

Karl H Weisgraber