The Cyclosporine story

Topic:David Moore's Medical Mycology blog

Discovery of cyclosporine in 1971 began a new era in immunopharmacology. It was the first immunosuppressive drug that allowed selective immunoregulation of T cells without excessive toxicity. Cyclosporine was isolated from the fungus Tolypocladium inflatum. Cyclosporine was first investigated as an anti-fungal antibiotic but its spectrum was too narrow to be of any clinical use. J. F. Borel discovered its immunosuppressive activity in 1976. This led to further investigations into its properties involving further immunological tests and investigations into its structure and synthesis. Cyclosporine has unwanted side effects, notably nephrotoxicity. Animal testing showed cyclosporin to be sufficiently non-toxic to begin clinical trials. These initially failed due to poor absorption of the drug. Once this had been overcome, results were encouraging enough for cyclosporine to be licensed for use in clinical practice. There is some controversy between Borel and other workers over priority in the discovery of cyclosporine and its pre-clinical development, which is examined in this review. Cyclosporine changed the face of transplantation. It decreased morbidity and enabled the routine transplantation of organs that until then had only been done experimentally.

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