| STUDY |
A potential new drug discovered by Co.'s scientists significantly prolonged survival rates of organ transplants in animals, without the side effects of current anti-rejection drug therapy. The Co.'s report shows that the new oral drug restrains the activity of an enzyme, JAK 3, a key signaling molecule in the immune response, and could therefore prevent organ rejection in humans who undergo organ transplants. More than 200,000 transplant-recipients in the United States are on life-long medical treatment to prevent organ rejection. Current anti-rejection therapy suppresses the immune system with a cocktail of drugs including cyclosporin and steroids, the long-term use of which has been shown to cause kidney damage, hypertension, atherosclerosis, and diabetes. Patients are prescribed antihypertensives and antihyperlipidemics to counter these side effects. This anti-rejection regimen has been shown to improve one-year survival rates of transplant recipients but has not been shown to ensure their long-term survival. "In spite of numerous treatment options for organ transplant and autoimmune disease patients, there remains a need for effective and safe immunosuppressive agents," said the research team leader (see author), Principal Research Investigator in the Department of Antibacterials and Immunology at Co., and leader of the research team which also included scientists from Stanford University School of Medicine, and the National Institutes of Health. JAK3 is a cellular enzyme, a kinase, which regulates the critical pathways involved in cell growth, activation and death. It signals a family of six growth factors in white blood cells to begin various cell activities, such as differentiation and proliferation. In blocking these functions, the JAK3 inhibitor stops the activation and reproduction of white blood cells that would reject a transplanted organ. Patients with Severe Combined Immunodeficiency Disease (SCID), or 'Bubble Boy Syndrome,' for example, lack functional immune systems due to a genetic defect in their JAK3 enzyme. Where JAK1 and JAK2 are ubiquitous, JAK3 is expressed in white blood cells. The Co.'s researchers hypothesized that by inhibiting the activity of the JAK3 enzyme in organ transplant recipients, they could suppress the human body's natural response to a foreign object, thus preventing rejection of a transplanted organ. They designed a compound, which in laboratory tests was highly potent for JAK3 inhibition, resulting in immune-suppression, while less potent for JAK1 and JAK2, which could result in serious side effects. In initial studies with mice receiving heart transplants, the compound suppressed a robust immune response. Most recently, Compd. was shown to prevent rejection in non-human primates receiving kidney transplants. The efficacy of the Co.'s compound in these studies was superior to that seen in parallel studies using cyclosporin, the current mainstay of therapy in transplant patients. "Our findings clearly establish that an orally available JAK3 inhibitor produces sufficient immune suppression by itself to prevent organ transplant rejection without inducing many of the side effects observed with current therapies," said author. Compd. was tolerated well in phase I safety studies in healthy human volunteers. The company is investigating the compound in the autoimmune disease, psoriasis, before proceeding to studies in patients with kidney transplants. The compound is the first potential medicine in the class of transplant rejection for Co. |
| UPDATE | 30.10.2003. |
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