Impel technology being used to develop countermeasure against chemical threat agent exposure

Impel NeuroPharma is has been engaged in developing countermeasures against chemical threats through various US government programs over the last few years. One of the areas we have been focusing on is an intranasally delivered Oxime for nerve agent exposure. Nerve agents belong to a class of compounds known as organophosphate (OP) agents. OP nerve agents, such as sarin gas, soman, tabun or VX, enter the blood stream via inhalation or absorption through the skin. The nerve agents travel in the circulatory system to the brain and muscles causing the nerves to become over-stimulated which lead to massive convulsions and death in severe cases. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the blood-brain-barrier to enter the brain. Because of this oximes are not very effective in preventing nerve agent-induced seizures.
Impel’s technology allows the countermeasure to access the brain and an Oxime-POD could be a new product included in a kit that also contains a systemic delivery option for Oximes (such as an intramuscular injection). The great thing about Impel’s product is that it can be administered easily self-administered on the field or administered by a first responder, if necessary, even if the subject is unconscious.

Last month, one of our collaborators at the Uniformed Services University, Bethesda (Federal medical school) published a report showing that one particular oxime known as Obidoxime could successfully protect the brain from and the neurotoxic effects of a nerve agent and also completely prevent mortality when administered intranasally using the Impel POD (Precision Olfactory Delivery) system.

The figure above comes from the article, featuring the distribution data with two molecules, 2PAM and Obidoxime. You can read it on Pubmed here (PMID: 26751814).

This group led by Dr. Namboodiri, observed an effect, both as a pretreatment, when obidoxime administered 30 mins before exposure to nerve agent and also when administered 5 mins after nerve exposure. A neuroprotective effect was demonstrated both at the molecular level by measuring acetylcholine esterase activity and at the cellular level by studying neurodegenerative changes. At the functional level, a significant reduction in both the severity and duration were observed. Among the oximes that this group tested and the ones Impel had studied earlier in a DoD grant, it was shown that all of these molecules achieved penetration in the brain. However, only one of these molecules was able to achieve efficacy in the brain. Thus providing further evidence that the ultimate success of an intranasally delivered drug depends on the properties on the physical and chemical properties of that drug.

While our collaborators continue to work on in vivo studies to further test this and other countermeasures, Impel continues to develop the clinical delivery technology so that it can be tested in humans on the field. Hopefully some day soon there will be a new or more effective line of defense against chemical threat agents on the battlefield.

Once developed the Obidoxime POD could also be a used to respond to the hundreds of thousands of insecticide poisoning suicides happening worldwide every year.[/vc_column_text][/vc_column][/vc_row]