Cornell University

Metabolon, Inc.

Other

Duke University

Dana-farber-cancer Institute Inc.

Avicena Group, Inc.

Amira, Inc.

Mayo Foundation for Medical Education and Research

The University of Chicago

Lipomics Technologies, Inc.

The General Hospital Corporation

Children's Hospital Research Center at Oakland

Ixcela, Inc.

Matabolon, Inc.

Fal Diagnostics

Rima Kaddurah-Daouk

Bruce S Kristal

Donald W Kufe

Richard M Weinshilboum

Ralph R Weichselbaum

Thomas W Bell

Jonathan J Burbaum

Alisher B Khasanov

Beverly A Teicher

M Flint Beal

K Ranga Rama Krishnan

James W Lillie

Rebecca Ann Baillie

Ghaleb Daouk

Wayne R Matson

Paul R Schimmel

Ronald M Krauss

Matthew W Mitchell

Liewei Wang

Anne M Evans

K Ranga R Krishnan

Theodore S Widlanski

Michiaki Kubo

Craig J Forsyth

Taisei Mushiroda

Steven M Watkins

Lisa A Paige

Don Harvan

Joseph P McEvoy

David Carl Steffens

Joanna Biernacka

Michelle M Wiest

Mark Frye

Madhumita Patnaik

Balmiki Ray

Fahad Mohammed Saleh Al Athel

Robert Kingston

Michael Green

Scott D Putney

Materials and methods for treating major depressive disorder by modulating the aryl hydrocarbon receptor system are provided herein.

Modulating the aryl hydrocarbon receptor system to treat major depressive disorder

The present invention has utilized the power of lipidomics to profile lipid metabolites and to characterize changes in lipid metabolism as they relate to CNS disorders. Lipidomic signatures can guide the development of diagnostic, prognostic and surrogate markers for CNS disorders; identification of new targets for drug design based on highlighted perturbed pathways; stratify patients with CNS disorders as to which pathways are impaired, and facilitate the determination of which patients with CNS disorders are candidates for a particular therapy, i.e. provide the tools for a personalized approach to therapy; identify which patients are responding or are developing side effects to a treatment; design of modified antipsychotics that have less metabolic side effects and enhanced activity; overcome the lag phase in response to some treatments; and find better combination therapies for CNS disorders that target the pathways that are impaired (e.g., impairments in lipid and/or carbohydrate metabolism).

Lipidomics approaches for central nervous system disorders

The present invention provides various biomarkers of depression. The present invention also provides various methods of using the biomarkers, including methods for diagnosis of depression, methods of determining predisposition to depression, methods of monitoring progression/regression of depression, methods of assessing efficacy of compositions for treating depression, methods of screening compositions for activity in modulating biomarkers of depression, methods of treating depression, as well as other methods based on biomarkers of depression.

Biomarkers for depression and methods using the same

The present invention concerns the application of lipidomics to statin treatment for disorders such as cardiovascular disorders. Hence, the invention provides, among other things, a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject following commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen. The invention further provides a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject before commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen.

Lipidomic approaches to determining drug response phenotypes in cardiovascular disease

The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy of drugs are also discussed.

Methods for drug discovery, disease treatment, and diagnosis using metabolomics

Methods for drug discovery disease treatment, and diagnosis using metabolomics

The invention provides methods of screening to identify compounds that modulate the ability of a protein to translocate to the mitochondria when a cell is subjected to cellular stress. Such compounds can be useful to modulate the level of apoptosis in a cell. For example, compounds identified according to the methods described herein can be used to treat disorders characterized by excessive apoptosis, e.g., a neurological disorder, or insufficient apoptosis, e.g., cancer.

Induction of apoptosis by cellular stress

The present invention relates to the use of creatine compounds including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system. Creatine compounds can be used as therapeutically effective agents against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer's disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine; (3) creatine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

Use of creatine or creatine analogs for the treatment of diseases of the nervous system

Growing community of inventors

Belmont, MA, United States of America

Rima Kaddurah-Daouk