Potent compounds for the treatment of nerve gas and pesticide exposureTechnology #cu13316
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International and domestic terrorism has been on the rise, prompting fears about large-scale attacks on civilian and soldier populations with chemical warfare being especially worrying due to the ease of production, transport and distribution of agents such as sarin gas. The current state of the art for treating exposure to organophosphates involves administration of atropine and pralidoxime (oxime reactivators), yet are often ineffective as they do not cross the blood brain barrier (BBB), have toxic intermediates, and require high concentrations that are extremely difficult to achieve in vivo. This technology has identified a class of small molecules that are capable reversing the effects of organophosphate exposure at much lower concentrations and has the ability to cross the BBB to treat the devastating central nervous system effects. The technology promises to bring peace of mind to populations at risk of terrorist attacks and pesticide poisoning.
A broad class of small molecules that are cheap and easy to produce
Organophosphates are highly toxic compounds found in pesticides and nerve agents, and work by inhibiting the enzyme acetylcholinesterase (AChE). This technology describes a deceivingly simple class of molecules that can effectively reverse the inhibition. The simplicity makes the compounds cheap and easy to produce in large quantities, and have proven to be safe in doses required for treatment. Furthermore, the molecules have been shown to prevent toxicity when given prophylactically, as well as inhibiting other enzymes such as butyrylcholinesterase (BuChE), further enhancing the utility of the technology.
The efficacy and safety of the technology was demonstrated in vivo in mouse models and in vitro with both mouse and human AChE enzymes. The crystal structure of the enzyme-compound complex has been solved and serves as a foundation for further studies into this broad class of molecules.
- Reactivation of acetylcholinesterase (AChE)
- Reactivation of butyrylcholinesterase (BuChE)
- Biodefense for counter-terrorism
- Treatment for exposure to organophosphates (pesticides)
- Basic neurological research tool
- Combinatory approach with other AChE re-activators to increase efficacy
- Potential prophylactic for high-risk areas and individuals such as soldiers in combat, cities with known terrorist activities and agriculture workers
- Prophylactic and post-exposure treatment of AChE inhibition
- Lower doses that are achievable in vivo
- Ability to cross BBB to treat central nervous systems (CNS) effects
- Ability to reactivate other enzymes such as BuChE
Patent Pending (WO/2014/113495)
Tech Ventures Reference: IR CU12165, CU12231, CU13083, CU13316