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New Important Link Identified Between Obesity and Diabetes

 
  October, 29 2002 15:58
your information resource in human molecular genetics
 
     
Myriad Genetics, Inc. (Nasdaq: MYGN), announced today that it has discovered a novel gene that causes human obesity. Myriad scientists led by Drs. Steven Stone and Donna Shattuck and University of Utah collaborators Drs. Steven Hunt and Ted Adams have named the gene HOB1, for Human Obesity 1, in recognition of its direct causal tie to obesity in humans. The HOB1 gene is a breakthrough discovery of an important gene for a complex genetic disorder. In addition, HOB1 appears to provide an important molecular link between obesity and diabetes. The discovery of HOB1 forms a necessary first step towards the development of novel therapeutics to treat a condition that, in moderate to severe forms, affects nearly one third of Americans.

The HOB1 gene is the first obesity gene discovered that is significantly involved in human obesity. Previous obesity-related genes have only been found to be an important cause of genetic obesity in mice or other animal models.

"The HOB1 gene appears to be powerful evidence of the role of heredity in the cause of obesity," said Donna Shattuck, Ph.D., Vice President of Metabolic Disease Research for Myriad Genetics, Inc. "The association with diabetes is also intriguing and sheds light on the known clinical association between the two disorders. The potential exists to address both conditions with a therapeutic development program based on HOB1."

Polygenic diseases such as obesity were thought to be prohibitively complex and unyielding to discovery by molecular techniques. With this discovery, Myriad has demonstrated that, using its proprietary technologies coupled with multi-generational Utah family pedigrees and medical databases, complex diseases with multiple contributing factors can be untangled and the causative elements identified.

The HOB1 gene's role in diabetes was demonstrated through Myriad's protein interaction and drug target discovery technologies. Myriad's high-throughput, industrial-scale protein interaction technologies have developed a diabetes disease pathway that involves a network of over 300 human proteins. Myriad scientists discovered that the HOB1 gene was directly involved in the diabetes pathway and that it interacted with a key protein in the pathway.

Myriad has also identified structural and biological characteristics of this gene, which have predicted functions that make it readily amenable to assay development for small-molecule drug discovery. In addition, the HOB1 gene appears to be a highly druggable target, in part because the mutation in the gene that contributes to serious obesity appears to result in a gain of function rather than a loss of function. In drug development, it is generally far easier to block a drug target than to replace its lost function.

The HOB1 gene is in pharmaceutical development at Myriad. High-throughput screening assays for small molecule drugs are being developed. These assays will be run against Myriad's proprietary library of over 200,000 small molecular weight compounds. Therapeutic rights to the novel HOB1 gene are owned exclusively by Myriad and have not been licensed to another party.

Recently introduced prescription medications intended to help individuals manage their weight have demonstrated limited efficacy and less than ideal tolerability. Similarly, despite a tremendous medical need, the pharmaceutical industry has enjoyed only limited success developing therapeutics to manage diabetes. The most common therapeutics, sulfonylureas, are not widely effective and the most promising new drugs, thiazolidinediones, have demonstrated rare but potentially fatal side effects. There is an urgent need for more comprehensive understanding and more effective therapies for these metabolic disorders.

As a predictive medicine product, HOB1 may also offer an opportunity to identify the genetic basis of an individual's obesity and to define the associated risk of developing type 2 diabetes in the future. Such information may provide the grounds for prevention and differential treatment of affected individuals. Diabetes prevention has recently been demonstrated to be effective among individuals at high risk of the disease. A major clinical trial from the Diabetes Prevention Program studied the value of diet and exercise in 3,234 people with impaired glucose tolerance, a condition that often precedes diabetes. Participants randomly assigned to intensive lifestyle intervention reduced their risk of getting type 2 diabetes by 58 percent. On average, this group maintained their physical activity at 30 minutes per day, usually with walking or other moderate intensity exercise, and lost 5-7 percent of their body weight.

About Obesity and Diabetes

Eighty million Americans are obese, or nearly one third of U.S. adults over the age of 20. The prevalence of obesity has steadily increased over the years among nearly all racial/ethnic groups. The total annual cost to the healthcare system of obesity is now estimated at $99 billion. In addition, Americans spend $33 billion annually on weight-loss products and services.

Diabetes is a disease in which the body does not produce or properly use insulin, a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. Type 2 diabetes is usually associated with obesity and is caused by resistance to insulin as well as the inability of the pancreas to keep up with the increased demand for insulin. Type 2 diabetes accounts for 90 to 95 percent of diabetes. Type 2 diabetes is nearing epidemic proportions, due to a greater prevalence of obesity and sedentary lifestyles. Recent research shows an alarming surge in children diagnosed with type 2 diabetes. In 1990, fewer than 4 percent of childhood diabetes cases were type 2. Today, according to the American Diabetes Association (ADA), that number has risen to approximately 20 percent of childhood type 2 diabetes, varying from 8 percent to 45 percent, depending on the age of the group studied and the racial/ethnic mix of the group studied. Of the children diagnosed with type 2 diabetes, 85 percent are obese.

Most children are diagnosed with type 2 diabetes during middle-to-late puberty. Physicians fear that as the childhood population becomes increasingly overweight and less active, more type 2 diabetes may occur in younger pre-pubescent children. Children who are less active, overeat, and have a family history of diabetes are most at risk of contracting type 2 diabetes. The cost of type 2 diabetes that is related to obesity is $63 billion, which is more than 60 percent of the total cost of type 2 diabetes.

The ADA estimates that approximately 15.7 million people, or 5.9 percent of the population, have diabetes. It is the seventh-leading cause of death in the United States.

Myriad Genetics, Inc. is a leading biopharmaceutical company focused on the development of novel healthcare products. The Company has established two wholly owned subsidiaries. Myriad Pharmaceuticals, Inc. develops and intends to market therapeutic products, and Myriad Genetic Laboratories, Inc. develops and markets proprietary predictive medicine and personalized medicine products. The Company has established strategic alliances with Abbott, Bayer, DuPont, Eli Lilly, Hitachi, Novartis, Oracle, Pharmacia, Roche, Schering AG, Schering-Plough and Syngenta.

The discussion in this news release includes forward-looking statements that are subject to certain risks and uncertainties, including statements relating to the clinical association between obesity and diabetes, the ability to address both obesity and diabetes with a therapeutic program based on HOB1, the druggability of HOB1, the opportunity provided by HOB1 to identify the genetic basis of an individual's obesity and to define associated risk of developing type 2 diabetes in the future. Such statements are based on management's current expectations that are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by forward-looking statements, including, but not limited to uncertainties as to the extent of future government regulation of Myriad Genetics' business, uncertainties as to whether Myriad Genetics and its collaborators will be successful in developing, and obtaining regulatory approval for, and commercial acceptance of, therapeutics; the risk that markets will not exist for therapeutic compounds that Myriad Genetics develops or if such markets exist, that Myriad Genetics will not be able to sell compounds, which it develops, at acceptable prices. These and other risks identified in the Company's filings with the Securities and Exchange Commission, including the Company's Annual Report on Form 10-K for the fiscal year ended June 30, 2002. All information in this press release is as of October 29, 2002, and Myriad undertakes no duty to update this information unless required by law.

SOURCE Myriad Genetics, Inc.

CONTACT: William A. Hockett, Vice President of Corporate Communications
of Myriad Genetics, Inc., +1-801-584-3600, bhockett@myriad.com

URL: http://www.myriad.com
http://www.prnewswire.com

Copyright (C) 2002 PR Newswire. All rights reserved.


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