SCIENTISTS DISCOVER DIFFERENCES OF KEY HUMAN DRUG METABOLIZING ENZYME

Researchers suspect new clues about human drug metabolism
may reveal insights into adverse drug reactions

Contact:
John Cashman, Ph.D.
Human BioMolecular
Research Institute
(858) 458-9305
jcashman@hbri.org

San Diego, Calif. (December 20, 2001)—Human BioMolecular Research Institute (HBRI), a leading non-profit research institute, announced today that its study conducted jointly with SEQUENOM™, Inc. (Nasdaq: SQNM), a discovery genetics company, has been reported in the December issue of Drug Metabolism and Disposition. Findings link a defective human enzyme, flavin-containing monooxygenase (form 3), to the abnormal metabolism of chemicals and drugs. These findings elucidate important clues to the mechanism of population differences in the susceptibility to abnormal metabolism or adverse drug reactions for chemicals metabolized by the flavin-containing monooxygenase (form 3), according to John Cashman, Ph.D., HBRI Director and lead author of the publication.

Research findings were reported by investigators of Human BioMolecular Research Institute, and Andreas Braun, M.D., Ph.D. and James Leushner, Ph.D. from SEQUENOM using SEQUENOM’s MassARRAY™ technology.

FMO3 is a key human drug and chemical metabolizing enzyme that influences the biotransformation and disposition of many drugs and chemicals. Although FMOs have been studied for more than 35 years, the molecular basis for its variable action remains elusive. The report shows that a considerable amount of enzyme variability is due to genetic differences.
"This paper provides important new information on genetic polymorphisms in various ethnic groups in expression of an drug metabolizing enzyme in human liver," said David E. Williams, Ph.D., Professor of Environmental and Molecular Toxicology at Oregon State University. "The benefits of this study are that it soon may be possible to rapidly screen individuals genetically and determine which FMOs they express in order to optimize therapeutic dosages of drugs for the FMO that plays a major role in metabolism."

The study, funded in part by the National Institute of General Medical Sciences of the National Institutes of Health and the University of California Tobacco-Related Disease Research Program, expands previous studies suggesting that variable metabolism of dietary amines was a function of differences in genetics of human genes, investigated the role of genetic variation in FMO3 in different populations.

About HBRI: The Human BioMolecular Research Institute is a non-profit research institute conducting basic research focused on unlocking biological and chemical principles related to diseases of the human brain. The institute conducts fundamental studies of central nervous system disorders and translates findings into new drug development to address human illness. In addition, the institute promotes scientific learning through community service and public access by disseminating information and sharing research with collaborators, colleagues and the public. For more information, visit www.HBRI.org.

About SEQUENOM: SEQUENOM is a discovery genetics company with the tools, information and strategies for determining the medical impact of genes. Utilizing a novel population genetics approach, SEQUENOM is systematically identifying potential disease-related genes that affect significant portions of the overall population. This approach is possible due to the pinpoint accuracy and unique specificity of the Company’s MassARRAY system. By focusing on disease genes with a broad population impact, SEQUENOM expects to play an important role in bringing new therapeutic products to the market while maximizing the return on drug development