Johns Hopkins University

Rusk Intellectual Reserve Ag

Akira Sawa

David A Kass

Neelam Shahani

Youjin Chung

Koko Ishizuka

YeeWen Candace Wu

Elki Takimoto

Toshiaki Saito

Nao J Gamo

Biomarkers relevant to neurons in the brain, in particular at single cell levels, are identified by using olfactory neurons as the best surrogates from subjects so as to establish diagnosis, prognosis, and treatment of brain conditions.

Methodology to identify biomarkers relevant to neurons in the brain by using non-invasive nasal biopsy

In DN-DISC1 mice, a mouse model for major mental illnesses, the model that expresses pathological phenotypes relevant to schizophrenia, mood disorders, and addiction simultaneously, the inventors of the present invention found pronounced levels of oxidative stress in the prefrontal cortex, but not in the striatum. These mice also displayed greater amounts of GAPDH-Siah1 binding, a protein-protein interaction that is activated under exposure to oxidative stress. The present inventors investigated the role of oxidative stress in other organ systems. As detailed herein, the inventors found that GAPDH-Siah1 binding was increased in mouse models of cardiac failure. It was also found, that certain novel analogs of deprenyl, significantly inhibited GAPDH-Siah1 binding in cardiac tissue. Thus, with experimental data provided herein, it is clear that this GAPDH-Siah1 binding cascade is a crucial mechanism involved in major mental illness, such as schizophrenia, mood disorders, and addiction, as well as in stress-associated diseases involving other organs where GAPDH is expressed. The present invention provides compounds and composition comprising analogs of deprenyl and their use in the inhibition of nuclear GAPDH-Siah1 binding and the activation of p300 and MEF2. Also provided herein are methods of prevention and treatment of stress induced disorders of the body, including, for example, major mental illness, such as schizophrenia, mood disorders, and addiction, as well as in stress-associated diseases involving other organs, such as cardiac hypertrophy, in vivo, comprising administering to a mammal a therapeutically effective amount of analogs of deprenyl.

GAPDH cascade inhibitor compounds and methods of use and treatment of stress induced disorders including mental illness

The present invention provides a method for diagnosing or predicting susceptibility to a psychiatric disorder in an individual, which comprises confirming molecular diversity and/or subcellular distribution of DISC 1 in the cell from the individual. In addition, a novel risk haplotype of DISC1 for psychiatric disorder is also provided.

Method for diagnosing or predicting susceptibility to psychiatric disorders

Growing community of inventors

Baltimore, MD, United States of America

Akira Sawa