We recently discovered a small molecule (‘piper-X’) that has the potential to be a broad-acting enhancer of counter-measures against nerve gas. We have evidence that piper-X inhibits the vesicular ACh transporter (VAChT), which pumps ACh into pre-synaptic vesicles. Piper-X therefore reduces ACh release into the synaptic cleft. We have evidence that piper-X can counteract the effects of both organophosphate and carbamate AChE inhibitors.
By lowering the abundance of ACh that is released into the synapse, piper-X holds promise as a broad-spectrum enhancer of current counter-measures, regardless of the chemical structure of the AChE poison. Hence, our work is poised to greatly increase the capacity to treat personnel and civilians who are attacked with nerve gas.
Nerve gas attack is an ever-present threat from rogue nations and terrorist organizations. There is a clear need to improve counter-measures against nerve gas attack due to the limitations of the currently available kits in the market, including that they work against only a limited number of organophosphate poisons. Nerve gas is the colloquial term used for small molecule inhibitors of acetylcholinesterase (AChE), an enzyme that breaks down the key neurotransmitter acetylcholine (ACh). ACh is rapidly removed from the synapse by AChE to maintain sensitivity of the post-synaptic cell to ACh signaling. Upon AChE inhibition, synaptic ACh levels increase, causing seizure, paralysis, and loss of respiratory drive.
Organophosphate or carbamate compounds are also used as insecticides and herbicides in the agriculture and farming industries. Accidental exposure to toxic levels of organophosphate or carbamate-based insecticides or herbicides may occur to the farmworkers.
- It will reduce ACh accumulation at the synapse regardless of the type of nerve gas exposure and is not time-dependent;
- The molecule is predicted to cross the blood- brain barrier and has the potential to protect the CNS from long-term damage;
- There is potential of using piper-X in combination with already available kits to further decrease toxicity concerns.
- IP: A provisional patent application was filed October 2019