Greater than 5 million Americans with pain unresponsive to current treatments
St. Louis, MO, September 18, 2000 - The National Institutes of Health (NIH) has awarded a six-month $290,000 Small Business and Innovation Research (SBIR) grant to MetaPhore Pharmaceuticals to study potential new treatments for managing both acute and chronic pain.
The grant will allow St. Louis-based MetaPhore to proceed with studies on pain using the company's patented metal-based compounds. The compounds mimic the body's primary defense mechanism against oxidative damage from the free radicals derived from oxygen known as superoxide. That defense mechanism in its natural state is a family of enzymes called superoxide dismutase (SOD).
The research will study the role of free radicals in pain and develop the SOD mimetics as potential drugs for pain relief, either administered alone or along with other drugs. Previous studies have shown that the SOD mimetics are effective in reproducing the natural enzyme's ability to reduce free radical formation, which has been linked to a number of diseases and conditions, including pain and inflammation.
"There is a tremendous need for new, non-opiate drugs for pain management, for the millions of patients whose pain is unresponsive to current treatment or who suffer from the known side effects of current pain medications," said Dr. Daniela Salvemini MetaPhore's Director of Biology and the Principal Investigator for the SBIR grant. "Extensive preliminary data and in vivo research indicates that SOD mimics hold excellent potential for development in these areas."
Pain is a growing health problem that affects a third of all Americans. Approximately 10 percent of the American population have pain that does not respond well to current therapies. These patients include those with acute, inflammatory and especially neuropathic pain which is generated by causes such as diabetes, AIDS, trauma and cancer chemotherapy.
Dr. Salvemini received her Ph.D. under the mentorship of Sir John Vane (winner of the 1982 Nobel Prize in Medicine for his work in the field of pain and inflammation) and worked at Monsanto/Searle before joining MetaPhore. She will be joined in this collaborative effort by Dr Frank Porreca, Professor of Pharmacology and Anesthesiology at the University of Arizona Health Sciences Center, a recognized expert in pain research who has worked closely with innovative chemistry in efforts aimed at the development of novel therapies for pain. Other members of the research team include Dr. Dennis Riley of MetaPhore and Dr. Micheal Ossipov of the University of Arizona Health Sciences Center.
Background on Free Radicals, SOD and MetaPhore's SOD Mimic
The formation of free radicals is a naturally occurring process. An excess of these reactive oxygen-derived molecules damages cell structure and even genes -- much like oxidation causes metal to rust. This type of progressive damage has become increasingly linked to several diseases and conditions, particularly those associated with aging such as auto-immune disorders like Parkinson's and rheumatoid arthritis, multiple types of cancer, as well as pain and inflammation.
The SOD enzyme, which is an essential protein mapped in the body's DNA, removes free radicals by converting the undesirable superoxide molecules into hydrogen peroxide and oxygen. This product of SOD's catalytic action also has potential benefits that complement those of free radical removal. Hydrogen peroxide has been shown to be critical to the functioning of white blood cells in killing foreign bacteria.
"SOD mimetics have major medical potential, based on the growing body of antioxidant and disease research. For more than twenty years, we have understood the free radical fighting power of the body's natural SOD enzyme, but until recently, we have been unable to reproduce the beneficial effect in a stable and selective drug form," said Dennis Riley, MetaPhore's Vice President of Research & Development.
Just like the antioxidant vitamins E and C, MetaPhore's SOD mimetics remove free radicals. However, the metal-based mimetic compounds do so at a greatly enhanced rate (mopping up more than 20 million superoxide molecules per second) and in a very selective manner. Unlike naturally derived SOD enzyme, the metal-based mimetic is well suited for use as a drug because it has a much lower molecular weight, is much more stable, has a longer half-life, and does not appear to elicit an immune response in the body.
Attempts to use natural, bovine-derived SOD enzymes in clinical applications were frustrated by the natural form's inherent instability and the body's allergic reaction to its introduction. It also had a very short half-life, lasting intact in the body only about fifteen minutes.
Numerous animal studies over the last few years have confirmed the disease fighting potential of MetaPhore's SOD mimetics. The October 1999 issue of Science published research documenting that MetaPhore's SOD mimetic substantially reduced tissue damage due to inflammation and reperfusion - the latter involving the return of blood flow to an organ following removal of a blockage, such as after a heart attack.
A study published in the Proceedings of the National Academy of Sciences in August 2000 indicated potential new treatments to counter the perplexing and often fatal blood pressure drop that accompanies septic shock.
The company's first drug candidate is targeted at cancer, where it is proceeding toward an Investigational New Drug (IND) submission to the FDA by year-end. The second drug candidate, for acute and chronic pain, is expected to move into clinical trials in the first half of 2001.
Among the other areas where MetaPhore is moving its SOD mimetics program forward are dermatitis, rheumatoid arthritis and stroke. The company believes its novel approach could result in treatments with unmatched therapeutic value, either on their own or as adjunct therapy with existing medications, and with minimal side effects.
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.