University of California

The General Hospital Corporation

Agenebio, Inc.

University of Michigan

Nicholas James Mayhew

Robert Jason Herr

Emily Elizabeth Freeman

Qin Jiang

John Anthony Butera

Graham Johnson

Rudolph Emile Tanzi

William C Mobley

Jianxing Huang

Belew Mekonnen

Steven L Wagner

Hemantbhai Patel

Ronald Buckle

Kevin D Rynearson

Neil Moss

James A Shayman

Scott D Larsen

Kim Hutchings

Zohreh Sajjadi Hashemi

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with CNS disorders. It also relates to the use of an α5-containing GABAreceptor agonist (e.g., an α5-containing GABAreceptor positive allosteric modulator) in treating cognitive impairment associated with CNS disorders in a subject in need or at risk thereof, including age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI, Age-Associated Memory Impairment, Age Related Cognitive Decline, dementia, Alzheimer's Disease (AD), prodromal AD, PTSD, schizophrenia, bipolar disorder, ALS, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease, autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of an α5-containing GABAreceptor agonist (e.g., an α5-containing GABAreceptor positive allosteric modulator) in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with CNS disorders. It also relates to the use of an &#x3b1;5-containing GABAreceptor agonist (e.g., an &#x3b1;5-containing GABAreceptor positive allosteric modulator) in treating cognitive impairment associated with CNS disorders in a subject in need or at risk thereof, including age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI, Age-Associated Memory Impairment, Age Related Cognitive Decline, dementia, Alzheimer's Disease (AD), prodromal AD, PTSD, schizophrenia, bipolar disorder, ALS, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease, autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of an &#x3b1;5-containing GABAreceptor agonist (e.g., an &#x3b1;5-containing GABAreceptor positive allosteric modulator) in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

Glucosylceramide synthase inhibitors and therapeutic methods using the same

Provided herein are compounds and methods for treating a disorder associated with aberrant A&#x3b2; peptide levels, including Alzheimer's disease.

Potent gamma-secretase modulators

Provided herein are compounds and methods for treating a disorder associated with aberrant A3 peptide levels, including Alzheimer's disease. Provided herein are compositions and methods for treating a disorder associated with aberrant A&#x3b2; peptide levels, including AD. Provided herein are compounds of Formula (A) or a pharmaceutically acceptable salt thereof, wherein, L' is selected from the group consisting of C(O), C(R1)(R2), substituted or unsubstituted &#x2014;C2-6 alkylene-, and substituted or unsubstituted &#x2014;C3-6 cycloalkylene. 

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Niskayuna, NY, United States of America

Nicholas James Mayhew