New Antifungal Drug Discovered
A drug which is almost always used in the treatment of chest pain or angina might be the key to a brand new process in fighting the deadly fungal illness cryptococcosis. This was according to scientists who studied the said drug.
Researchers from the University of Birmingham came across in their studies that the drug fendiline hydrochloride would be used to stimulate a patient’s white blood cells to fight the fungal infection in an effective way, as a substitute for using medicinal drugs that directly kill the fungus itself. The findings of this study were published in the International Journal of Antimicrobial Agents. This study suggest a function for calcium-channel blockers corresponding to fendiline hydrochloride as inhibitors to the survival of Cryptococcus neoformans, the pathogen which causes cryptococcosis, and represent a promising method for future anticryptococcal drug design and therapy.
Professor Robin from the University of Birmingham mentioned, Fungi are intrinsically more difficult to target than bacteria, because they are much more closely related, evolutionarily, to humans. Finding an essential pathway in a fungus that you could inhibit, which doesn’t exist in humans, is very difficult. Therefore the approach of stimulating your own immune system to kill the fungus, instead of killing it directly through treatment, is potentially more powerful.
To bring about illness, Cryptococcus neoformans hides inside the sufferer’s own white blood cells, making it primarily difficult to treat. Within the Birmingham Drug Discovery establishment, the researchers screened 1,200 off-patent, FDA-accepted, medicines to determine candidates that probably may be redeployed to battle with cryptococcosis by triggering the white blood cells to recognise that they’re infected and to kill the fungus that hides within them.
After preliminary screening, 19 of these compounds within the Prestwick Chemical Library® of the FDA-accredited small molecules showed promise for significantly decreasing intracellular growth of the pathogen.
Secondary screening and host cell toxicity tests ruled out many of these molecules, but highlighted fendiline hydrochloride, which is more commonly used in the remedy of angina and chest soreness, as a potential candidate for the development of future anticryptococcal therapies.
Professor May mentioned, Although calcium channel blockers have not previously been identified as a potential anticryptococcal agent, their ability to work in this way makes sense. We have previously shown that Cryptococcus perturbs calcium signalling when living inside human cells, probably in order to trick the cell into not killing it. Consequently, it’s possible that fendiline hydrochloride works by overcoming this perturbation and restoring normal calcium dynamics, helping the host to kill the fungus.
Cryptococcosis neoformans poses a predominant risk to immunocompromised sufferers and is a main killer of HIV patients worldwide.
HIV/AIDS sufferers are particularly inclined to cryptococcal infections, with an estimated overwhelming disease burden of about 1,000,000 circumstances of cryptococcal meningitis per year. The best possible incidence of cryptococcal meningitis associated deaths in HIV-positive sufferers occurs in sub-Saharan Africa with a related mortality of 70%.
The disease starts off with inhalation of infectious agents (spores or dessicated yeasts) leading to a predominant pulmonary infection, which will additionally disseminate to the nervous system thus inflicting meningitis.
Cryptococci are primarily complex to treat with antifungal drugs as a result of their ability to manipulate and exist inside the host’s body.
Dr Rebecca Hall from the University of Birmingham remarked, Considering the poor status of current anticryptococcal drugs, new treatment options for cryptococcosis are much needed. Though the relatively high dose of fendiline hydrochloride required renders it unfit for clinical deployment against cryptococcosis in itself, our study presents an opportunity to approach treatment of this much neglected disease in a new way.