Elan Pharmaceuticals, Inc.

Elan Pharma International Limited

Prothena Biosciences Limited

Athena Neurosciences, Inc.

The Flinders University of South Australia

The Trustees of Flinders University

John P Anderson

Sukanto Sinha

Guriqbal Basi

Varghese John

Jay S Tung

Lisa Claire McConlogue

Gwen Tatsuno

Normand Frigon

Minh Tam Doan

Michael Power

Shuwen Wang

Jason Marc Goldstein

Tamie Chilcote

Pamela S Keim

Dean R Artis

Yong-Liang Zhu

Simeon Bowers

Roy K Hom

R Jeffrey Neitz

Anh P Truong

Marc Adler

Donald Walker

Jennifer Sealy

Lisa Clair McConlogue

Hua Tan

Xiaocong Michael Ye

Robert Galemmo

Paul Beroza

David Chereau

Kelly Banducci

Kirsten L Jacobson-Croak

Irene Griswold-Prenner

Robert A Galemmo, Jr

Susanna M S Chrysler

Normand L Frigon, Jr

Irene Griswold

Susanna M Chrysler

Tami J Chilcote

Tamie J Chilcote

Dean Richard Artis, I

Wei Ping Gai

Wei Ping c/o Department Of Human Physiology Gai

Danielle L Aubele

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

Antibodies to alpha synuclein

The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, E, E, R, R, Rand Rare defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Inhibitors of polo-like kinase

The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, X, R, R, R, R, Rand Rare defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

The invention provides agents and methods for treatment of diseases associated with Lewy body diseases (LBDs) in the brain of a patient. Preferred agents include inhibitors of PLK2 kinase.

Alpha-synuclein kinase

The invention provides agents and methods for treatment of diseases associated with Lewy body diseases (LBDs) in the brain of a patient. Preferred agents include inhibitors of PLK2 and GRK6 kinases.

Disclosed is an active, isolated &#x3b2;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (APP and APPsw) are also disclosed. These compositions are useful for use in methods of selecting compounds that modulate &#x3b2;-secretase. Inhibitors of &#x3b2;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

&#x3b2;-secretase enzyme compositions and methods

Disclosed are various forms of an active, isolated &#x3b2;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (&#x3b2;-APPwt and &#x3b2;-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate &#x3b2;-secretase. Inhibitors of &#x3b2;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Beta-secretase enzyme compositions and methods

Truncated fragments of alpha-synuclein in Lewy body disease

Disclosed are various forms of an active, isolated &#x3b2;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (&#x3b2;-APPwt and &#x3b2;-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate &#x3b2;-secretase. Inhibitors of &#x3b2;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Compositions comprising a novel protease capable of cleaving &#x3b2;-amyloid precursor protein (APP) on the amino-terminal side of the &#x3b2;-amyloid peptide therein are provided. The protease is designated &#x3b2;-secretase. Reaction systems comprising &#x3b2;-secretase may be used in screening assays to monitor &#x3b2;-secretase modulated cleavage of APP and to identify &#x3b2;-secretase inhibitors, wherein the &#x3b2;-secretase is in the presence of a suitable polypeptide substrate and cleavage of the substrate determined in the presence and absence of the test substance. Antibodies are raised against peptides of &#x3b2;-secretase. Pharmaceutical compositions and methods comprise compounds identified by screening assays.

Methods and compositions for inhibiting &#x3b2;-secretase

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San Francisco, CA, United States of America

John P Anderson