The grant will help fund further preclinical studies that MetaPhore is conducting with its proprietary family of superoxide dismutase (SOD) mimetics, one of which was shown in earlier studies to improve heart function in animal models of heart attack. The funding is the fourth SBIR grant the company has received to date, following earlier grants to study the potential use of SOD mimetics for pain, refractory hypotension and cancer.
A heart attack is a primary example of an ischemic event, in which a blockage restricts blood flow to the heart, leading to damage and tissue death within the heart. In recent years, there has been substantial progress in treating such blockages, for example, with fast-acting, clot-busting drugs. However, it is also known that further damage occurs when blood flow is re-established to tissues – a condition known as reperfusion injury.
To counter this “second wave” of damage in ischemic events, some researchers have focused on the role of superoxide, a naturally-occurring free radical that, in excess, has been shown to be involved in various destructive processes. Following an ischemic event, the renewed inflow of blood triggers an overproduction of superoxide, which damages proteins and DNA in tissue cells. The damaged tissue dies, leading to scar tissue and reducing the heart’s ability to function.
In previous preclinical studies on superoxide and ischemic heart disease, researchers at MetaPhore and Wake Forest University Baptist Medical Center tested one of MetaPhore’s small-molecule SOD mimetics – developed to replicate the action of natural SOD enzymes and remove excess superoxide – in animal models of cardiac reperfusion injury. Those preclinical studies showed that when the SOD mimetic was administered prior to the re-opening of blood vessels in the heart following an ischemic event, damage to heart tissues was reduced and heart function was markedly improved. Under the NIH grant, MetaPhore will study a recently developed and highly active SOD mimetic as a potential drug candidate for ischemic heart disease. The research also will be designed to provide additional mechanistic information on the role of superoxide in reperfusion injury, findings that may also apply to other ischemic events, such as strokes.
“Cardiovascular diseases remain the leading cause of death in the U.S. While there has been much progress with thrombolytic therapies for ischemic heart disease, there is still a tremendous need to develop new therapies that can limit the damage that occurs as a result of reperfusion,” said Daniela Salvemini, Ph.D., MetaPhore’s Vice President of Pharmacology and principal investigator for the grant. “As superoxide appears to be a significant mediator of damage during ischemic events, SOD mimetics could offer an effective strategy to protect heart tissues and preserve heart function.”
Dr. Salvemini will be joined in the project by researchers from Wake Forest, including R. Mark Payne, M.D., as co-investigator.
Background
MetaPhore Pharmaceuticals has developed a fundamentally new approach to pharmaceutics – small molecule mimics of an essential human enzyme. MetaPhore’s first clinical candidates from this approach target some of the most significant human medical needs. These include refractory hypotension, certain types of cancer, pain, andinflammation.
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. For example, 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 small size, are highly stable and do not appear to cause 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.
MetaPhore Pharmaceuticals is a privately-held drug research and development company based in St. Louis, MO. 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.