Cognosci, Incorporated

Duke University

Other

Biozyme, Inc.

Cognosei, Inc.

Michael Peter Vitek

Dale J Christensen

Daniel T Laskowitz

Suzanne E McKenna

Anthony Cerami

Peter C Ulrich

Richard J Bucala

Helen Vlassara

Christopher Self

Allen D Roses

Xini Zhang

J Brice Weinberg

Jeanne F Loring

Marcia Moss

William E VanNostrand

Carol A Colton

Jessica Oddo

Noriaki Mitsuda

Feng-Qiao Li

Carol Anne Colton

Fred H Rasmussen

Judianne Davis

Hana N Dawson

The present invention provides novel pharmaceutical compositions comprising ApoE-derived peptide dimers. In particular, the ApoE peptide dimers of the invention comprise at least two ApoE mimetic domains and can comprise one or more protein transduction domains. Methods of treating various conditions, such as cancer, inflammatory conditions, and neurodegenerative diseases, by administering the pharmaceutical compositions of the invention are also disclosed.

ApoE peptide dimers and uses thereof

The present invention provides methods for modulating SET activity by contacting SET with a binding agent such as an ApoE peptide derivative. In one embodiment of the invention, a pharmaceutical composition capable of modulating SET activity is administered to a patient for the treatment of an inflammatory or neurological condition. In another embodiment of the invention, compounds efficacious for the treatment of inflammatory and neurological conditions are identified by screening for a binding agent capable of competing with or inhibiting the binding of an ApoE derivative to SET.

Methods for decreasing set in inhibiting protein phosphatase 2A (PP2A) and/or increasing the activity of cyclin-dependent kinase 5 (CDK5) by an APOE peptide

A modified non-human warm-blooded vertebrate animal in which a biologically active human APP polypeptide is expressed, and in which function of its inducible Nitric Oxide Synthase (iNOS) protein is reduced as compared to a non-modified animal, methods of making the animal, and methods of testing a candidate composition for activity in the treatment of Alzheimer's Disease using the animal.

Model of Alzheimer's Disease

The present invention provides a method of modulating calcineurin activity in a cell by contacting the cell with at least one ApoE analog. Methods of treating various disorders associated with calcineurin activity using one or more ApoE analogs are also disclosed. In particular, the present invention provides a method of reducing demyelination and promoting remyelination in a subject. Methods of treating spinal cord or nerve injury in a subject are also described.

Methods of inhibiting calcineurin with ApoE analogs

Provided are methods of predicting or assessing the level of severity of cancer or cancer progression in a patient comprising measuring levels of SET expression in a biological sample from a patient and comparing levels of SET expression to a control sample or standard value. Methods for predicting or evaluating the efficacy of a SET therapeutic and kits comprising at least one reagent for measuring SET protein expression are also provided.

Methods of diagnosing cancer

Novel ApoE peptide derivatives and ApoE-protein transduction domain conjugates are disclosed which are useful for treating disorders including CNS inflammation, traumatic brain injury, inflammatory bowel disease (also known as Crohn's Disease or ulcerative colitis), cerebral ischemia, atherosclerosis, sepsis, multiple sclerosis and arthritic diseases, Alzheimer's Disease and other brain disorders. The invention encompasses methods for protecting subjects having undergone irradiation or radiotherapy by administration of ApoE or at least one ApoE mimetic peptide.

ApoE analogs and methods for their use

Novel ApoE peptide derivatives and ApoE-protein transduction domain conjugates are disclosed which are useful for treating disorders including subarachnoid hemorrhage, intracerebral hemorrhage, and intraventricular hemorrhage and other brain disorders. The invention encompasses methods for treating cerebral vasospasm by administration of at least one ApoE or ApoE mimetic peptide.

Treatment of subarachnoid hemorrhage with ApoE analogs

Treatment of subarachnoid hemorrhage with Apo E analogs

Novel ApoE-protein transduction domain conjugates are disclosed which are useful for treating disorders including CNS inflammation, traumatic brain injury, cerebral ischema, Alzheimer's Disease and other brain disorders.

APO E analogs and methods for their use

Methods for determining matrix metalloproteinase (MMP) activity in biological samples are described. The methods of the invention are useful to assess disease severity or progression, diagnose a particular disease, or develop a profile of MMP activity for inflammatory diseases such as arthritis, or cancer. The methods of the invention involve the use of particular amino acid sequences in substrates to measure the activity in biological samples of MMP's including collagenase 3, stromelysin 1, gelatinase A, gelatinase B and collagenase 1. A diagnostic kit for use in determining the amounts of MMP activities in biological samples is also provided.

Assays for measuring matrix metalloproteinase activities

A bigenic mouse is provided whose germ cells and somatic cells contain (i) inactive mouse TAU genes, and/or (ii) a transgene encoding the human TAU gene, with the transgene including all regulatory elements of the human TAU gene necessary for neuronal expression of the transgene in the bigenic mouse, and/or for human patterns of expression of the transgene in the bigenic mouse. The mice of the invention may contain one or two alleles for the human TAU gene (i.e., one or two TAU alleles). Mice of the invention are useful as a source of human Tau protein, and are useful as a model of Alzheimer's, Frontal Temporal Dementia and Parkinson's-like diseases.

Transgenic mouse expressing human tau gene

A method of treating cells that carry at least one APOE4 allele comprises increasing nitric oxide levels in the cells (e.g., by administering an exogenous source of nitric oxide to the cells) by an amount sufficient to combat the decrease of nitric oxide level associated with the presence of the APOE4 allele. Also disclosed is a method of increasing nitric oxide levels in cells in need thereof which comprises administering APOE to the cells in an amount sufficient to increase nitric oxide levels in the cells.

Modulation of nitric oxide production

The present invention relates generally to the non-enzymatic glycosylation of amyloidogenic proteins and the consequent formation of advanced glycosylation endproducts (AGEs). It has been found that formation of AGE-amyloidogenic proteins can enhance amyloidosis. The invention further relates to compositions and methods for the prevention and treatment of amyloidosis associated with amyloid diseases, particularly neurodegenerative disease and Type II diabetes, and more particularly Alzheimer's disease. In a specific example, aggregation of an amyloidogenic peptide, &bgr;AP, is enhanced by the glycosylation reaction of &bgr;AP to form AGE-&bgr;AP as defined herein. Accordingly, the invention extends to a method for modulating the in vivo aggregation of amyloid polypeptides and associated amyloidosis by controlling the formation and presence of AGE-amyloid polypeptide. A corresponding diagnostic utility comprises the measurement of the course and extent of amyloidosis by a measurement of the presence and amount of AGEs and particularly, AGE-amyloid. An assay is included that may use the AGE-amyloid polypeptide of the present invention to identify disease states characterized by the presence of AGE-amyloid. Additionally, such an assay can be utilized to monitor therapy and thus adjust a dosage regimen for a given disease state characterized by the presence of AGE-amyloid.

Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis

An isolated DNA molecule that directs neuron-specific transcription of a downstream heterologous DNA segment (a promoter segment) in a mammalian cell is disclosed. The isolated DNA molecule contains a promoter segment from the mouse genomic Presenilin-1 DNA, or a DNA sequence that hybridize to such DNA and directs neuron-specific transcription of a downstream heterologous DNA segment in a mammalian cell. DNA constructs comprising such promoter segments and various uses thereof are also disclosed.

Growing community of inventors

Cary, NC, United States of America

Michael Peter Vitek