New Treatments/ Preventive Measures For Fungal Infections

Three classes of anti-fungal drugs currently exist ¹ : 

1.  Polyene drugs such as Amphotericin B.
2. Azole drugs such as voriconazole, fluconazole, itraconazole, ketoconazole, and posaconazole.
3. The newly developed echinocanadin drugs such as caspofungin and micafungin.

All of these drugs have difficulties due to lack of coverage for all fungi and the development of fungal resistance in fungi that were previously treatable by the drug.  Some of these antifungal drugs- such as amphotericin B- also have serious problems with toxicity side effects.

Clearly, new treatments for fungal infections are needed.  Several new promising fungal treatments/ preventive measures include vaccines, Blad containing oligomers, and dihyroorotate dehydrogenase inhibitors.  These new treatments are described briefly below:

Vaccines- No clinically available vaccines currently exist for fungal diseases ². Mouse studies using live, attenuated fungi such as Blastomyces dermatititidus and Cryptococcus neoformans have shown promising results ². Some human studies involving formaldehyde killed spherules of Coccidioides immitis or recombinant Candida albicans proteins have been somewhat promising ².  

Blad Containing Oligomers.  These chemicals are derived from the Lupinus (lupine) plant.  These Blad Containing oligomers are able to inhibit growth of Candida albicans by alteration of metal metabolism and by causing apoptotic cell death³. 

Dihydroorotate Dehydrogenase Inhibitors-  Recently, a new antifungal drug F901318 has been discovered which has strong inhibitory effects on many Aspergillus species including Aspergillus fumigatus, flavus, niger and terreus but does not seem very toxic to human cells.  These drugs block Aspergillus growth by inhibiting the enzyme dihydroorotate dehydrogenase which is involved in fungal DNA synthesis.

References / Sources

1. Oliver JD, Sibley GE, Beckmann N, et al. F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. Proc Natl Acad Sci U S A. 2016.

2. Armstrong-James D, Brown GD, Netea MG, et al. Immunotherapeutic approaches to treatment of fungal diseases. Lancet Infect Dis. 2017.

3. Pinheiro AM, Carreira A, Prescott TAK, Ferreira RB, Monteiro SA. Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi. Frontiers in microbiology. 2017;8:1182.

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