ST. LOUIS, June 27, 2000 -- The nearly 50,000 heart surgery patients who suffer severe problems after stents are inserted into their unclogged arteries are among the growing number Americans with medical implants who may benefit from a general anti-inflammatory surface treatment for biomedical materials reported for the first time today in the Journal of Biomedical Materials Research. Some estimates suggest that one in ten Americans may have a medical implant of some kind.
Researchers at MetaPhore Pharmaceuticals treated the surface of three commonly used device materials -- polyethylene, poly(etherurethane urea) and tantalum metal -- to allow permanent attachment of a new class of anti-inflammatory drugs, and then implanted the materials in a rat model. Examination of tissue surrounding the implant revealed a dose dependent anti-inflammatory effect, including:
- A dramatic reduction in both acute and chronic inflammation around the materials,
- A potent inhibitory effect on matrix production and fibrosis on the implant surface, and
- A protective effect on poly(etherurethane urea) biodegradation in vivo
"These dramatic results are, to our knowledge, the first description of a general anti-inflammatory surface treatment for biomedical materials," said Kishore Udipi of Metaphore Pharmaceuticals. Other members of the research team included: Denis Forster and Dennis Riley, also of Metaphore Pharmaceuticals and Richard L. Ornberg, Bruce Thurmond and Steven Settle of Searle.
The new class of anti-inflammatory drugs simulates -- or mimics -- the natural enzyme superoxide dismutase (SOD), which combats superoxide ions secreted by white blood cells in the body in its efforts to break down a material implant. Unchecked, the secretion of superoxide ions, as well as digestive enzymes, results in the implant's degradation and loss of function as well as chronic inflammation and fibrotic capsule formation.
Superoxide is a free radical arising from oxygen metabolism in activated white cells. SOD catalyses the removal of superoxide radicals providing a major protective effect in our bodies.
Unlike the natural enzyme, the mimic of SOD is well suited for use as a protective surface treatment for biomaterials because it has a low molecular weight, remarkable oxidative and kinetic stability, and heat stability up to 350 degrees. The SOD mimic used in this research is not a protein like the natural form, but instead is a specially constructed manganese-based compound.
Attempts to use natural, bovine-derived SOD enzyme in clinical applications have been 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.
"Mimics of SOD have major medical potential. For over twenty years we have understood the inflammation fighting power of the SOD enzyme but we have been unable to reproduce the beneficial effect in a stable drug form. We have now achieved this and can safely and dependably reproduce the superoxide fighting effect in numerous animal models, enabling us to address a myriad of therapeutic areas", said Dennis Riley, MetaPhore's Vice President of Research & Development.
In October 1999, Science Magazine published research documenting that MetaPhore's mimic of SOD substantially reduced tissue damage due to inflammation and reperfusion -- the latter involving the return of blood flow to a surgical site following a surgical procedure. These results provided a scientific rationale for an entirely new class of molecules based on the mimic of SOD to treat inflammation, pain, shock, arthritis and the side effects associated with chemo and radiation therapy.
Located in St. Louis, MetaPhore Pharmaceuticals, Inc., is applying its metal-based technology platform to develop novel therapeutics addressing significant unmet medical needs. The company's proprietary expertise in rational drug design and metal-based therapeutics has been used to explore novel approaches to iron-overload, antibiotics and antioxidants. The company's most advanced program is in the antioxidant area with proprietary mimics of the body's own radical fighting enzyme, superoxide dismutase. MetaPhore is moving its superoxide dismutase mimetics forward for inflammation and pain, dermatitis, refactory hypertension and reperfusion injury. MetaPhore believes its approach to superoxide dismutase mimetics could result in treatments with unmatched therapeutic value and minimal side effects. Additional information is available at http://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.
Journal
Journal of Biomedical Materials Research