Antidote ‘vaccine’ may protect against attacks

Your chest feels tight and you find it hard to breathe. As you start convulsing, you lose control of your bodily functions. The effects of nerve agents are truly gruesome and can be lethal within minutes unless an antidote can be given quickly.

But what if you could get a transfusion that renders the deadly chemical non-toxic before you go into battle?

Researchers in the US, China and Saudi Arabia developed a vehicle that stabilises as otherwise short-lived nerve agent antidote so it can neutralise the effects of the chemicals.

The stabiliser – which is a zirconium metal-organic framework, or MOF – was published in ACS Nano.

Nerve agents are among the most toxic chemical weapons, according to the US Centres for Disease Control and Prevention.

They’re colourless, all but odourless and can be sprayed in an aerosol or as a gas. As little as a millilitre on skin can kill within a few minutes unless an antidote is administered. It’s no wonder they’re classified weapons of mass destruction by the UN.

A nerve agent’s power stems from their ability to interfere with chemical messages transmitted by nerves to organs, muscles and other nerves.

Acetylcholine is one such “neurotransmitter” chemical. Once it’s released by a nerve cell to, for instance, trigger a muscle cell to contract, it’s usually rapidly broken down by an enzyme called acetylcholinesterase.

When the acetylcholine signal has disappeared, the muscle cell relaxes again.

But nerve agents block acetylcholinesterase so muscles stay contracted, brain function is warped and eventually, an afflicted individual dies unless they have antidote on hand.

There are a few types of antidote, such as another enzyme called organophosphorus acid anhydrolase that chops up nerve agents. But time is of the essence. Could prevention be better than cure?

Injections of organophosphorus acid anhydrolase are quickly cleared by a body’s immune system. And encapsulating them in biodegradable nanocarriers has kept them round for around two days, but those carriers are unstable, and difficult to store and handle.

Peng Li from Northwestern University and colleagues thought metal-organic frameworks could be a stable protective casing for organophosphorus acid anhydrolase.

Metal-organic frameworks, as their name suggests, are metal ions or clusters with organic (carbon-based) links that form regular crystal structures. They’re highly porous, meaning they’re perfect for trapping and hanging onto molecules.

The smallest enzyme-loaded crystals performed best, breaking down the diisopropyl fluorophosphate in two minutes.

So Li and his crew made zirconium metal-organic framework crystals of different sizes, then soaked them in organophosphorus acid anhydrolase before dropping them in a solution (with a pH of 7.2, similar to blood) and added the nerve agent simulant diisopropyl fluorophosphate.

The smallest enzyme-loaded crystals – which were only 300 nanometres long – performed best, breaking down the diisopropyl fluorophosphate in two minutes. This was more than three times faster than free organophosphorus acid anhydrolase.

The team then tried the metal-organic framework crystals with soman, a nerve agent in the same family as sarin. They saw the same result – the 300-nanometre crystals cleared it away three times faster.

Of course, it’s still early days, the researchers admit. They only tested soman – not other nerve agents such as sarin or VX.

Nor do they know how long the crystals will last in real blood – their fake blood was a buffer solution. And the crystals will need modifying so if they are injected into the bloodstream, the immune system doesn’t toss them out too. But, they write, they’re working on it.