According to a paper published on 2 January in Science Translational Medicine, ‘nanoscavengers’ or ‘bioscavengers’ may offer an effective treatment against the highly toxic nerve agents used in chemical attacks (1). The new therapy may be able to provide long-lasting protection to at-risk populations. Moreover, nanoscavengers hold promise as a preventative treatment against organophosphate-based pesticide poisoning, which causes tens of thousands of deaths each year in the developing world.
Nerve agents were first discovered accidentally in the 1930s by researchers searching for cheaper and more effective insecticides. Two forms ― tabun and sarin ― were later developed by German chemists just before the start of World War II. The volatile, colourless liquids were too toxic for commercial agricultural use but soon became known as potential chemical weapons as they were found to cause death to humans by disrupting the central nervous system, even in minuscule quantities.
The deadly substances are part of a dangerous chemical family of organophosphorus compounds and can cause death within minutes when exposed to the skin or inhaled. They work by binding to acetylcholinesterase, an enzyme that catalyses the breakdown of acetylcholine, a neurotransmitter used to send messages between cells involved in muscle contraction. The subsequent deadly buildup of acetylcholine in the synapses quickly leads to tightening of the chest, difficulty breathing, seizures, and very soon after, death by asphyxiation or cardiac arrest. Other symptoms of nerve gas exposure include vomiting and incontinence.
Chemical attacks during the Iran-Iraq war of the 1980s, the Tokyo sarin subway attack in 1995, and other more recent deadly attacks, including the use of chemical warfare in Syria’s ongoing civil war, highlight the urgent need for better countermeasures. The most effective antidotes, such as atropine, block acetylcholine receptors but must be administered immediately to reverse the effects of nerve gas, and can only mitigate the symptoms. Furthermore, once nerve agent molecules do bind to acetylcholinesterase, they form an irreversible bond. It can take the body weeks to generate new enzymes for recovery if it does at all.
Scientists from the University of Washington, the U.S. Army Medical Research Institute of Chemical Defense, and Texas A&M University have now developed nanoparticle-based bioscavengers that break down some types of nerve agents, such as sarin and tabun, into innocuous compounds. Since the organophosphorus compounds are ‘scavenged‘ in the bloodstream before intoxication, bioscavengers could prevent potential side effects and remove the need for rapid administration of antidotes.
The researchers showed that animals were protected from repeated exposure to sarin for one week after just a single administration. Previously, bioscavengers have only been shown to provide protection for a few hours after administration. This time, the team of researchers wrapped them in a polymer gel to create nanometer-sized organophosphate-targeting particles that can stay in the body for much longer.
The findings suggest that these new nanoscavengers may be an effective preventative treatment for populations at risk of nerve agent poisoning. In the future, one dose of an effective bioscavenger may protect those vulnerable for weeks or even months. Of course, the treatments will first need to be tested in larger animal models and subsequent clinical trials but could someday prevent lifelong brain damage or death after exposure to even the deadliest of nerve agents.
(1) Zhang, P. et al.Nanoscavenger provides long-term prophylactic protection against nerve agents in rodents. Science Translational Medicine (2018). DOI: 10.1126/scitranslmed.aau7091