Medinox's NOX-100 is Identified as New Treatment to Prevent Rejection of Translplanted Organs
Results of preclinical study, published in Transplantation and the Journal of Cardiovascular Pharmacology also show that NOX-100 reduces risk of side effects from Cyclosporine A
SAN DIEGO, CA. March 20, 2000 -- Researchers at the Medical College of Wisconsin in Milwaukee utilized a novel combination therapy of NOX-100, a new experimental drug being developed by Medinox, Inc. of San Diego, and cyclosporine A (CsA) as a new therapeutic approach to prevent rejection of transplanted organs.
The Wisconsin studies showed that the NOX-100 + CsA combination therapy allowed long-term survival of transplanted organs, as well as reduced the CsA dose needed to prevent rejection by 75%.
CsA, a well known and widely used anti-organ rejection drug, has toxic side effects. At doses needed to prevent rejection, CsA can be toxic to the heart and kidney.
In this new approach, NOX-100 may allow transplant patients to receive the benefits of anti-rejection drugs such as CsA without suffering their toxic side effects.
Further details can be found in the original articles in Transplantation (Volume 69, pp. 227-231) and in the Journal of Cardiovascular Pharmacology (Volume 35, pp. 114-120).
Transplantation is a life-giving procedure that can extend the lives of patients with organ failure. Due to advances in surgical procedures and rejection-preventing drugs, the number of organ transplants is increasing each year. According to United Network for Organ Sharing (UNOS), nearly 22,000 organ transplant were performed in the US in 1998.
Placing a donated organ into the body, however, can provoke a response from the immune system. This is because the body's immune system identifies a transplanted organ as a foreign invader and attacks it.
During this response, the immune system produces nitric oxide in abundance. Nitric oxide is a reactive molecule that the body uses as a weapon against foreign invaders. When directed against pathogens, nitric oxide can destroy viruses and bacteria. When directed against the transplant, nitric oxide causes tissue damage that can result in the death of the transplanted organ.
In the Wisconsin studies, the researchers conducted their evaluation of the new NOX-100 + CsA combination therapy in a rodent cardiac transplantation model. In addition to reducing the dose of CsA, the researchers observed that the combination therapy produced a tolerance-like effect which resulted in the exceptionally long-term survival of the transplants - even after treatment with the drugs was withdrawn.
Dr. Allan Roza, Professor of Surgery at the Medical College of Wisconsin, led the investigations. "Our studies established proof of concept for a new therapeutic modality that may reduce the potential for cyclosporine A toxicity as well as extend the survival of transplanted organs," remarked Dr. Roza. "The long-term survival and tolerance-like effect induced by the new combination therapy could have important implications for transplant patients."
On the study by the Wisconsin group, Dr. Monte Lai, Medinox's President & CEO, noted that "The studies by Dr. Roza and colleagues validated the use of Medinox's technology in transplantation and broadened the therapeutic possibilities for NOX-100. We are pleased to know that NOX-100 might also benefit the thousands of transplant recipients who must use cyclosporine A every day."
NOX compounds: New approaches to inflammatory diseases
NOX-100 is being developed from Medinox's broadly based nitric oxide neutralizer platform technology. The company's proprietary NOX compounds bind nitric oxide very tightly and with great specificity, preventing the bound nitric oxide from participating in processes that lead to disease pathology.
A key feature of NOX compounds is their ability to remove excess, pathology-causing nitric oxide while preserving the low level of production of the molecule that is vital for normal body functions. Medinox's "neutralizer" approach for eliminating excess nitric oxide is potentially more effective as a therapeutic than enzyme inhibitors, which block nitric oxide synthesis.
NOX compounds have potential application for many human diseases and disorders that involve excessive nitric oxide production. These inflammatory conditions include neurodegenerative diseases (Alzheimer's, Parkinson's diseases; multiple sclerosis), chronic inflammatory diseases (arthritis, psoriasis), Type I diabetes, nephritis, migraine headaches, and ischemia/reperfusion injury.
Clinical trials for NOX-100
In September, Medinox initiated a Phase I/II clinical trial at the University of California, San Diego Medical Center to evaluate how NOX-100 might alleviate the condition of intradialytic hypotension (IH) in hemodialysis patients. IH is the episode of low blood pressure that is the most common adverse side effect of routine hemodialysis. Numerous studies have implicated excessive nitric oxide production with this condition.
This spring, Medinox will also begin a Phase I/II clinical trial to test NOX-100's effectiveness for the treatment of sepsis. This spring, Medinox will also begin a Phase I/II clinical trial to test NOX-100's effectiveness for the treatment of sepsis.
As the leader in nitric oxide-neutralizing therapeutics, Medinox is applying its broad technology platform to the discovery and development of new medicines for a wide variety of human diseases and disorders. Additional therapeutic technologies are under development as novel approaches to chronic inflammatory disease.