Calcium-targeting drugs could potentially treat fatal cryptococcosis infections.
Researchers in a recent study found that fendiline hydrochloride, which is commonly used to treat angina, could potentially treat patients with a fatal cryptococcosis infection.
The drug may stimulate the patient’s white blood cells instead of using drugs to target the bacteria, according to a study published in the International Journal of Antimicrobial Agents. Cryptococcus neoformans hide in white blood cells and cause the infection, which makes it extremely hard to treat.
"Fungi are intrinsically more difficult to target than bacteria, because they are much more closely related, evolutionarily, to humans,” said researcher Robin May, MA, PhD. “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."
Researchers analyzed 1200 FDA-approved drugs to find candidates that could potentially cause infected white blood cells to kill the fungus inside of them. They found 19 candidates that could potentially do so, but additional screening and host cell toxicity assays removed many candidates.
Fendiline hydrochloride was eventually identified as a potential treatment.
"Although calcium channel blockers have not previously been identified as a potential anticryptococcal agent, their ability to work in this way makes sense,” Dr May said. “We have previously shown that Cryptococcus perturbs calcium signaling 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.”
Patients who inhale the spores or desiccated yeasts will likely develop a pulmonary infection that could reach the central nervous system and cause meningitis. Immunocompromised patients are prone to cryptococcal infections, especially patients with HIV/AIDS. In sub-Saharan Africa, the associated mortality is 70%, according to the researchers.
The study found that further research is needed to determine whether other calcium-targeting drugs could be used to fight this disease.
"Considering the poor status of current anticryptococcal drugs, new treatment options for cryptococcosis are much needed,” concluded researcher Rebecca Hall, PhD. "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."