Teaching old drugs new tricks: Reincarnating immunosuppressants as antifungal drugs

Jill R. Blankenship, William J. Steinbach, John R. Perfect, Joseph Heitman

Research output: Contribution to journalReview articlepeer-review

64 Scopus citations

Abstract

Invasive fungal infections are rising worldwide as the number of immunocompromised patients increases. Unfortunately, our armamentarium of antifungal drugs is limited. Although current therapies are effective in treating some of the most prevalent infections, the development of novel treatments is vital because of emerging drug-resistant strains and species and because of the toxicity of certain current therapies. The immunosuppressive drugs CsA (cyclosporin A), FK-506 (tacrolimus) and rapamycin (sirolimus) exert potent antifungal effects against a variety of pathogenic fungi. These compounds are all currently in clinical use as immunosuppressive therapy to treat and prevent rejection of transplanted organs. Rapamycin is also in clinical trials as an antiproliferative agent for chemotherapy and invasive cardiology. Recent studies reveal a potent fungicidal synergism between azoles and the calcineurin inhibitors CsA and FK-506, and animal studies demonstrate that the CsA-fluconazole synergistic combination has therapeutic benefit. Less immunosuppressive analogs have been identified with potential to enhance current therapies, or as monotherapy without deleterious effects on the immune system. In summary, these highly successful pharmaceutical agents may find an even broader clinical application in combating infectious diseases.

Original languageEnglish (US)
Pages (from-to)192-199
Number of pages8
JournalCurrent Opinion in Investigational Drugs
Volume4
Issue number2
StatePublished - Feb 1 2003

Keywords

  • Aspergillus
  • Candida albicans
  • Cryptococcus neoformans
  • Cyclosporin A
  • FK-506
  • Immunophilins
  • Rapamycin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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