News Release

Yamanouchi Pharmaceutical Co., Ltd.

Yamanouchi Invents a Method to Accurately Determine Internal Body Time and Rhytem Disorders Using DNA Chips -Research Results Published in the PNAS

July 20 ,2004

Tokyo, Japan - July 16, 2004 - The Molecular Medicine Laboratories (director: Masao Kato) of Yamanouchi Pharmaceutical Co., Ltd. (President & CEO: Toichi Takenaka) developed a new method to accurately determine internal body time and rhythm disorders using DNA chips in its genomic drug discovery research. The findings will be reported in the week of July 19 in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

In the study, a group of researchers from the company developed a method that makes it possible to accurately determine internal body time and rhythm disorders in single-time-point measurement using DNA chips that enables to analyze the expression of dozens of thousands of genes at a time. At first, the group comprehensively extracted, using DNA chips, genes that periodically change with circadian rhythms in clock- controlled organs (time-indicating genes). The group then developed a method to accurately determine internal body time and rhythm disorders based on the expression of these genes and validated the mechanism in animal experiments. This work has been conducted under the leadership of Hiroki R. Ueda of Yamanouchi Pharmaceutical Co., Ltd. (currently the Institute of Physical and Chemical Research) as part of the Development for Bio-molecular Network Analysis Project commissioned by the New Energy and Industrial Technology Development Organization (NEDO). The researchers obtained suggestions and advice from a number of research organizations, including Hokkaido University School of Medicine and the Institute of Physical and Chemical Research.

Suprachiasmatic nuclei located in the brain ticks away like the oscillator of a clock and controls 24-hour rhythms for various physiological functions, such as sleep, awakening, changes in blood pressure and body temperature, and hormone secretion. Typical diseases and symptoms that are caused when these rhythms are disturbed include sleeplessness, depression, jetlag, refusal to attend the school, and nocturnal poriomania, a symptom associated with dementia. More recently, these rhythms have been found to affect the efficacy of drugs. At present, patients must be constrained for at least 2 days in order to accurately determine internal body time. The research results reported by the Yamanouchi researchers make it possible to accurately determine the state of the biological clock using DNA chips at a single-time-point and open a way to the prevention and treatment of various diseases that are caused as a result of disorders of these rhythms.

Yamanouchi places top priority on genome-based technologies in drug discovery and is strengthening its in-house research systems and aggressively promoting strategic alliances with bioventure companies in Japan and abroad. A number of new drug discovery targets discovered through its genomic drug discovery research have already entered the preclinical research stage. The company is committed to further accelerating the acquisition of new genes and their use in drug discovery research in order to develop breakthrough drugs with unique mechanisms of action.


Reference

Title: Molecular-Timetable Methods for Detection of Body Time and Rhythm Disorders from Single-time-point Genome-wide Expression Profiles
Authors: Hiroki R. Ueda, Wenbin Chen, Yoichi Minami, Sato Honma, Kenichi Honma, Masamitsu Iino & Seiichi Hashimoto


Abstract

Title: Molecular-Timetable Methods for Detection of Body Time and Rhythm Disorders from Single-time-point Genome-wide Expression Profiles

Detection of individual body time (BT) via a single-time-point assay has been a longstanding unfulfilled dream in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To achieve this dream, we created a "molecular timetable" composed of >100 "time-indicating genes" whose gene expression levels can represent internal BT. Here we have described a robust method called the "molecular-timetable method" for BT detection from a single-time-point expression profile. The power of this method is demonstrated by the sensitive and accurate detection of BT and the sensitive diagnosis of rhythm disorders. These results demonstrate the feasibility of BT detection based on single-time-point sampling, suggest the potential for expression-based diagnosis of rhythm disorders, and may translate functional genomics into chronotherapy and personalized medicine.