MetaPhore's Enzyme Mimetic Compound Could Reduce Complications of Diabetes; Studies in British Journal of Pharmacology Show Removing Free Radicals is Key.

Business Editors & Health/Medical Writers

ST. LOUIS--(BW HealthWire)--Aug. 28, 2001

Severe, long-term complications of diabetes, a growing health problem that affects an estimated 16 million Americans, may be reduced with new treatments based on an 'enzyme mimetic' that has been shown to significantly improve the functioning of blood vessels and nerves in diabetic animal studies, as reported in the September issue of the British Journal of Pharmacology.

Most of the major complications of diabetes are due to vascular abnormalities -- in which blood flow is restricted and blood vessels of all sizes may be injured -- and damage to nerves throughout the body, known as diabetic neuropathy. Depending on the location of the damage, patients may suffer a wide range of complications -- including eye, foot and kidney problems.

The pre-clinical efficacy studies conducted by researchers at the Veterans Affairs Medical Center and the University of Iowa in Iowa City, Iowa and MetaPhore Pharmaceuticals, Inc. of St. Louis confirmed that an excess of free radicals -- particularly superoxide -- found in the vascular tissue of diabetic rats is a major factor in the development of vascular dysfunction and subsequent nerve damage.

To evaluate the role of superoxide free radicals in these conditions, researchers administered a superoxide dismutase (SOD) mimetic (M40403) to diabetic rats. M40403 is one of a proprietary family of small-molecule SOD mimetics developed by MetaPhore that are designed to replicate the action of natural SOD enzymes, one of the body's primary defenses against free-radical damage to cells and tissues.

The research showed that the SOD mimetic significantly improved blood flow to the nerves and restored normal relaxation of the vessels around the sciatic nerve, the principal sensory and motor nerve of the lower body. Treatment with M40403 also restored normal motor nerve conduction velocity -- the speed at which the motor nerves transmit signals from the brain.

"Vascular dysfunction and nerve damage affect both Type 1 and 2 diabetes patients, and are the main underlying factors for a host of serious, long-term complications," said principal investigator Mark A. Yorek, Ph.D., Associate Professor of Medicine in the Department of Internal Medicine at the University of Iowa and with the VA Medical Center in Iowa City. "By confirming the role of superoxide free radicals in diabetic vascular and nerve diseases, this research indicates a potentially significant new approach for treating and preventing many of these complications."

Currently, there is no treatment for diabetic neuropathy, which is estimated to affect nearly half of all diabetics after 25 years with the disease. Standard approaches for staving off diabetes-related damage to blood vessels and nerves consist of careful blood glucose monitoring and control measures, including dietary and lifestyle changes and drug therapy depending on the severity and type of the patient's diabetes.

According to the Centers for Disease Control and Prevention, diabetes is the sixth leading cause of death in the U.S. and one of the leading causes of ill health. Total costs related to diabetes have been estimated to approach $100 billion. Making prevention and treatment efforts difficult is the fact that up to half of the 16 million Americans with diabetes are undiagnosed. In addition, even with careful control of blood glucose levels, vascular and nerve damage is still likely to occur over time.

"Reducing the damage that diabetes does to blood vessels and nerves could significantly improve the quality of life for millions of diabetic patients," added Daniela Salvemini, Ph.D., Vice President and Director of Pharmacology of MetaPhore.

In addition to Drs. Yorek and Salvemini, other members of the research team included Lawrence J. Coppey, Jill S. Gellett, Eric P. Davidson, Joyce A. Dunlap, and Donald D. Lund, all with the University of Iowa and the VA Medical Center in Iowa City, Iowa. The research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, Veterans Affairs and the International Juvenile Diabetes Foundation.

Background

MetaPhore Pharmaceuticals is a privately held, St. Louis-based drug research and development company that is applying its proprietary enzyme mimetic technology to address the diseases and conditions associated with excessive superoxide free radical production. These include refractory hypotension, certain types of cancer, pain, and inflammation -- as well as complications of diabetes.

As part of the body's oxidative chemistry, SOD enzymes regulate normal levels of superoxide. Certain disease states, however, promote an overproduction of superoxide and the natural enzymes are overwhelmed. In excess, superoxide has been shown to contribute to inflammatory processes, inhibit certain disease fighting mechanisms and affect mechanisms involved in regulating vascular pressure.

MetaPhore scientists pioneered the design and development of SOD mimetics. Previous attempts by the pharmaceutical industry to develop a naturally-derived SOD drug showed promise; however, use of the drug, a bovine form of SOD, was frustrated by the enzyme's inherent instability and the immunologic response to the bovine protein.

The company's SOD mimetics are promising drug candidates because they have a low molecular weight, are highly stable and do not appear to elicit an immune response in the body. Furthermore, the chemical structure of the metal-based compounds can be easily optimized for application to different diseases and conditions.

MetaPhore is developing its family of enzyme mimetics as drug candidates for refractory hypotension, pain, inflammation and cancer, as well as other diseases and conditions associated with free-radical damage. The first of MetaPhore's drug candidates began human clinical trials this year.

"SOD mimetics have major medical potential, based on the growing body of research that links free radical-induced damage to numerous diseases and conditions. We can effectively replicate the beneficial action of the SOD enzyme in a stable and selective drug form, and also tailor specific mimetic compounds for each disease state," said Dennis Riley, Ph.D., Senior Vice President of Research & Development at MetaPhore.

For more information, please visit www.metaphore.com.

Statements in this press release that are not strictly historical are "forward looking" statements as defined in the Private Securities Litigation Reform Act of 1995. The actual results may differ from those projected in the forward looking statement due to risks and uncertainties that exist in the company's operations, development efforts and business environment.