Zengen Inc's scientists have discovered a novel approach to reduce organ rejection based on the Company's proprietary research with alpha-Melanocyte-Stimulating Hormone (a-MSH). The research shows that treatment with the a-MSH peptide caused a significant increase in allograft (transplanted tissue) survival and a marked decrease in leukocyte (or white blood cell) infiltration, one of the main causes of infection leading to organ rejection.
"These results demonstrate that the protection of the transplanted tissue from early injury with a-MSH treatment can postpone rejection," said James Lipton, chief scientific officer and director of Zengen. "This is an important and encouraging advance in the field of organ transplantation and these data provide strong support for the development of anti-rejection therapies utilizing our proprietary peptide molecules based on the larger a-MSH peptide."
The preclinical study was designed to determine whether a-MSH treatment protects the allograft and prolongs survival in experimental heart transplantation, in the absence of immunosuppressive therapies. Donor cardiac grafts (Brown Norway) were transplanted into the abdomen of recipient (Lewis) rats. Treatments consisted of intraperitoneal injections of the a-MSH peptide or saline from the time of transplantation until sacrifice or spontaneous rejection.
Results show that median survival time of the peptide-treated organs was significantly prolonged (10 days) as compared to the untreated ones (6 days) (p<0.0001). Histopathologic and gene expression patterns of allografts from treated animals, examined 24 hours after transplantation, revealed substantial benefit over untreated animals and persisted over time. At four days post-transplantation, graft histopathologic appearance was healthier in treated animals. Further, the research revealed that treatment with a-MSH caused a marked inhibition of ET-1 gene expression. ET-1 is the most potent endogenous vasoconstrictor yet identified and contributes to reperfusion injury, transplant rejection and several cardiovascular diseases.
"This is a remarkable increase in duration in non-immunosuppressed transplanted organs, as data from this study and others show that hearts transplanted in these animal models are invariably rejected within six to seven days," added Dr. Lipton. "The beneficial effects of a-MSH treatment observed in these studies could be even more pronounced in clinical transplantation, particularly with regard to its significant role in ET-1 inhibition. We are excited by these findings, especially as we advance our peptide technology program in organ transplantation."