University of Pennsylvania

Other

University of California

John Q Trojanowski

Virginia Man-Yee Lee

Kurt R Brunden

Amos B Smith, Iii

Carlo Ballatore

Dustin Covell

Kelvin C Luk

Xiaozhao Wang

Hank F Kung

Mei-Ping Kung

Zhi-Ping Zhuang

Daniel M Skovronsky

Francesco Piscitelli

Joshua Rokach

James H Eberwine

Donna Mary Huryn

Garret A FitzGerald

Adam T Hoye

Anne-Marie L Hogan

Onur Atasoylu

Edward Lee

Longchuan Huang

Michael James

James Soper

Donna M Huym

Domenico Pratico

Stephen Ginsberg

Killian Oukoloff

Sugiyama Shimpei

Ryong-Woon Shin

Virginia MY Lee

The present disclosure provides monoclonal antibodies that bind α-Synuclein. In certain aspects, the antibodies preferentially bind to α-Synuclein fibrils over α-Synuclein monomer. In other aspects, the invention comprises a method of treating α-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting α-Synuclein fibrils using any of the antibodies of the invention.

Monoclonal antibodies against alpha-synuclein fibrils

The present disclosure provides compounds of formula (I) or (II) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Rx-R8 are defined herein. Also provided are compositions comprising a compound described herein and a pharmaceutically effective excipient, methods of stabilizing microtubules in a patient comprising administering to the patient a microtubule-stabilizing amount of a compound described herein, methods of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein, and methods of treating a neurodegenerative disease in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein. 

Substituted [1,2,4]triazolo[1,5-a]pyrimidines for stabilizing microtubules

The present disclosure provides monoclonal antibodies that bind &#x3b1;-Synuclein. In certain aspects, the antibodies preferentially bind to &#x3b1;-Synuclein fibrils over &#x3b1;-Synuclein monomer. In other aspects, the invention comprises a method of treating &#x3b1;-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting &#x3b1;-Synuclein fibrils using any of the antibodies of the invention.

Monoclonal antibodies against pathological alpha-synuclein, and methods using same

The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.

Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies

The present invention is directed to compounds of formula I: wherein A is n is 0, 1, or 2; m is 0 or 1; Ris H or Calkyl and Ris H, Calkyl, Calkaryl, aryl, or heteroaryl; and X is O or NH. Tautomers, enantiomers, and diastereomers, as well as pharmaceutically acceptable salt forms, of compounds of formula I are also within the scope of the invention. Methods of preparing and using the compounds of formula I are also described.  

Cycloalkyl-dione derivatives and methods of their use

Provided is an antibody that selectively binds to an epitope formed by residues 1-11 of A&#x3b2; in an A&#x3b2; oligomer, a method comprising using the antibody to treat a disease characterized by such an A&#x3b2; amyloid deposit in a patient, and kits comprising same.

Antibody treatment of Alzheimer's and related diseases

The present invention relates to novel TP receptor antagonists, which optionally cross the blood-brain barrier of a mammal. The invention also provides methods for treating a disorder related to activation of TP receptor utilizing the compounds of the invention.

Thromboxane A2 (TP) receptor antagonists

The present invention is directed to carboxylic acid-containing pharmaceutical compounds where the carboxylic acid moieties have been substituted with cycloalkyl-dione derivatives, as well as tautomers and pharmaceutically acceptable salt forms thereof. These bioisosteric replacements improve the compound's ability to effectively cross the blood brain barrier and result in improved pharmacokinetic, toxicological, and/or safety profiles.

This invention relates to a method of imaging amyloid deposits and to labeled compounds, and methods of making labeled compounds useful in imaging amyloid deposits. This invention also relates to compounds, and methods of making compounds for inhibiting the aggregation of amyloid proteins to form-amyloid deposits, and a method of delivering a therapeutic agent to amyloid deposits.

Amyloid plaque aggregation inhibitors and diagnostic imaging agents

This invention relates to a method of imaging amyloid deposits and to labeled compounds, and methods of making labeled compounds useful in imaging amyloid deposits. This invention also relates to compounds, and methods of making compounds for inhibiting the aggregation of amyloid proteins to form amyloid deposits, and a method of delivering a therapeutic agent to amyloid deposits.

Provided are methods of assessing the absence or presence of a neurodegenerative disease in a subject comprising characterizing TDP-43 in a tissue sample of the subject. Also disclosed are methods for diagnosing a neurodegenerative disease in a subject, and methods for determining the efficacy of a drug against a neurodegenerative disease. Novel antibodies that bind to TDP-43 are also provided.

Detection of neurodegenerative disease

Methods of treating individuals suspected of suffering from diseases, conditions or disorders of the Central Nervous System including nerve damage are provided wherein stable, homogeneous post-mitotic human neurons are into the individual's brain or at or near a site of nerve damage. Pharmaceutical compositions of stable, homogeneous post-mitotic human neurons and a pharmaceutically acceptable medium are also disclosed. Methods of generating non-human animal models of human CNS diseases, conditions or disorders by implanting stable, homogeneous post-mitotic human neurons into the brain of a non-human animal are disclosed. Non-human animals eith stable, homogeneous post-mitotic human neurons implanted in their brain are also disclosed.

Compositions and methods for producing and using homogenous neuronal cell transplants

The invention includes methods useful for the diagnosis of Alzheimer's disease and the evaluation of enhanced levels of lipid peroxidation in a mammal. The methods utilize isoprostanes as sensitive and stable molecular markers for lipid peroxidation in a mammal. Methods of identifying compounds useful for the treatment of Alzheimer's disease or for reducing levels of lipid peroxidation in a mammal are also included. The invention also includes kits useful for the diagnosis of Alzheimer's disease and for the evaluation of levels of lipid peroxidation in a mammal.

Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases

Methods of detecting RNA in brain tissue of patients with Alzheimer's disease are provided. Methods of diagnosing Alzheimer's disease by detection of these RNAs are also provided.

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Philadelphia, PA, United States of America

John Q Trojanowski