Elan Pharmaceuticals, Inc.

Athena Neurosciences, Inc.

Other

Russell E Rydel

Eugene D Thorsett

Varghese John

Dale Bernard Schenk

Theodore A Yednock

Peter Andrew Seubert

Michael S Dappen

Kate Dora Games

Sarah Wright

Lisa Claire McConlogue

Lisa Clair McConlogue

Irene Griswold-Prenner

Irene Griswald Prenner

The present invention features methods and compositions for inhibiting amyloidogenic protein toxicity, inhibiting formation of an amyloidogenic protein deposit and/or treating amyloidogenic diseases by administering a pharmaceutically effective amount of one or more agents that bind an integrin or an integrin subunit.

Methods of inhibiting amyloid toxicity

The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzhe## disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the &#x3b2;-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the A&#x3b2; region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, &#x3b2;-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

Testing compounds for effects on synaptophysin in transgenic mice expressing an Alzheimer's disease FAD DNA sequence

The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzheimer's disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the &bgr;-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the A&bgr; region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, &bgr;-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

Method for selecting a transgenic mouse model of alzheimer's disease

Substituted pyrimidine compositions and methods of use

Arylsulfonamides which have the general structure: with the symbols R.sup.1, R.sup.2, R.sup.3, R.sup.4, A and n representing the groups and integers provided in the detailed description are provided herein. These compounds have activity as inhibitors of phospholipase A2, inhibitors of cytokine release and as inhibitors of neurodegeneration.

Arylsulfonamides as phospholipase A.sub.2 inhibitors

The invention is drawn to a method for identifying agents that inhibit neural degeneration by administering to cell populations consisting essentially of neurons or cells from neuronal cell lines, where these cells are exposed to an apoptotic stimulus other than APP gene products, an agent, where it is determined whether the agent inhibits neural degeneration.

Inhibition of phospholipase A.sub.2 to reduce neuronal cell death

The invention provides methods and compositions for treating neurodegeneration in mammalian cells by administering a phospholipase A2 inhibitor.

Growing community of inventors

Belmont, CA, United States of America

Russell E Rydel