In folklore and movies, silver is often one of the best tools against terrifying monsters like vampires and werewolves. But a recent study seems to show that silver could help defeat some real-life horrors, too. Silver nanoparticles loaded with common anti-seizure drugs might be able to safely and effectively treat brain-eating infections caused by amoebas, the study found.
Amoebas are incredibly flexible, single-celled protozoans, capable of creating finger-like protrusions from their body that let them crawl where they need to go. Typically, amoebas aren't the least bit interested in people, preferring to live in freshwater or the soil, where they feed on bacteria.
But when certain species of amoeba end up in a person's central nervous system and brain — usually by being inhaled through the nose from contaminated water — they can literally feast on the brain's tissues. This mind-nomming, coupled with the widespread inflammation brought on by the immune system desperately trying to fight the infection, eventually shuts down the brain, though not before sufferers experience severe headaches, a loss of smell and taste, hallucinations, and coma.
The most notorious of these infections (called primary amebic meningoencephalitis, or PAM) is caused by Naegleria fowleri, colorfully known as the brain-eating amoeba.
"These diseases are still considered rare but almost always result in the patient's demise," lead author Ayaz Anwar, a research fellow at Sunway University in Malaysia, told Gizmodo. "Unfortunately, to date there is no single drug available to treat these infections."
Indeed, there were only 30 cases of PAM recorded in the US from 2007 to 2017, according to the Centres for Disease Control and Prevention, with just three known survivors. And while doctors have deployed some experimental drugs against these infections, with seemingly good results, there remains no official treatment.
Part of what makes treating brain amoeba infections so hard is that antifungal drugs can't reach the brain easily from the bloodstream, thanks to the blood-brain barrier. While these drugs are sometimes used to treat these infections, the high doses needed to overcome the barrier can damage brain cells, and they often don't work.
But some drugs can cross the barrier and affect the central nervous system, like those that are used to treat seizure or anxiety. And Anwar and his team theorised that the right drugs could be retooled to combat PAM.
The three anti-seizure drugs that Anwar and his team decided to test out — diazepam (sold as Valium), phenobarbital, and phenytoin — are known to affect cell receptors found in both amoeba and humans. They decided to use silver nanoparticles as the delivery method, Anwar told Gizmodo, because of the metal's "inherent antimicrobial properties" and ability to be tolerated by the body, while the small surface area of the particles would allow more of the drug to reach the target.
Other studies of theirs had shown that antifungal drugs, packaged onto silver nanoparticles, were able to better kill off N. fowleri, adding support to their hunch.
The team doused petri dishes containing N. fowleri and another group of amoeba that can cause fatal brain infections, Acanthamoeba, with the drugs alone and in combination with the silver. And while all three drugs were able to kill the amoebas by themselves, their effectiveness was amplified by the use of the silver.
In later experiments with human cells, the team also found that the drug combinations largely left the cells alive (the Valium/silver combo, in particular, appeared to be entirely non-toxic to cells), while stopping the amoeba infection from spreading further.
The findings, published this month in ACS Chemical Neuroscience, are early. But studying these drugs — which are already often used to manage the neurological symptoms of a brain amoeba infection — has its perks, Anwar says.
"The best thing about using FDA-approved, clinically available drugs is that they are known to be safe and easier to procure, therefore in my opinion these are already having a head start," he said.
Studying potential treatments for rare diseases like PAM is certainly a challenge. And there's still a lot to figure out, including the best way to deliver a treatment to a patient. Since amoebas get in our brain through the nose, Anwar speculates that using a nasal spray to get the drugs up there would work just as well. For now, the team next plans to study how these drugs can work in actual living animals.