The Solution is CounterVail's Galantamine. With $5M in grants to date, pre-IND studies funded by the NIH and the US Army show that galantamine is far superior to currently available OP poisoning treatments. Galantamine is effective both as a prophylactic and in post exposure to these toxins. Countervail is in the enviable regulatory position of obtaining FDA clearance for another indication of an existing drug. This advantage will reduce both the time and money required to bring the product to market. Countervail owns the commercialization license for the application of galantamine as an OP antidote.
A key characteristic of galantamine is its ability to protect both the peripheral and central nervous systems (CNS). No other OP treatment has been shown to cross the blood-brain barrier to effectively protect the CNS. Studies show that without the protection of the CNS, brain tissue degenerates following OP exposure causing serious neural damage. Galantamine is available in both tablet and injectable dosage forms. The tablet is rapidly absorbed, has a long shelf life, can be packaged for easy forward distribution and is an ideal format for nerve gas prophylaxis in military personnel, first responders and downwind populations. The tablet is also a convenient dosage format for pesticide prophylaxis for the 1.8 billion farm workers at risk of OP exposure worldwide. The injectable form can be made available in an auto-injector delivery system for post OP exposure treatment of incapacitated victims.
To date, the Department of Defense and the National Institutes of Health have invested a total of $5M in grants to the University of Maryland for the development of this technology.
One of the more serious concerns in bio-terrorism includes the release of deadly nerve agents causing Organophosphorus poisoning (OP) due to such deadly nerve agents as Soman and Sarin. These toxicants irreversibly inhibit the acetylcholinesterase enzyme leading to loss of muscle control and adverse Central Nervous System (CNS) effects. These are quickly followed by coma and death.
Galantamine (currently approved for use in treating Alzheimers disease), reversibly inhibits acetylcholinesterase in the brain and periphery and effectively prevents seizures and neurodegeneration.
Nerve agents such as Soman and Sarin are among the most lethal chemical weapons ever developed and have been used with catastrophic results in wars and terrorist attacks.
Studies funded by the US Army and National Institute of Neurological Disorders and Stroke performed by the University of Maryland in conjunction with the US Army demonstrated the effectiveness of Galantamine in protecting against the acute toxicity of lethal doses of the nerve agents soman, sarin, VX and paraoxon. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of these agents effectively and safely counteracted their toxicity. The dosage required was well tolerated. In addition it was found that in preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. UMD has subsequently applied for a patent on the acute and prophylactic use of galantamine as an antidote for nerve gas applications.
In more recent studies the researchers found that animals treated with galantamine and later exposed to lethal doses of Soman or Sarin survived and showed none of the common symptoms of exposure such as convulsions, respiratory distress and loss of coordinated movement. Recent data suggests that Galantamine alone, when administered prior to or within 25 minutes post exposure can protect against not only the acute toxicity of lethal doses of nerve agents but also the neurological tissue destruction in brain tissue following exposure. These studies also indicate the efficacy of an oral tablet in lieu of a liquid injection.
A recent PNAS publication (Golomb, March, 18, 2008) underscores the immediate need for a more effective Nerve Gas Countermeasure with the following attributes:
Safety CNS
Protection
Extended Prophylaxis Extended Treatment
Fast Acting Improved Efficacy
Improved Ease of Administration Longer Duration of Protection
This is Countervail’s primary focus.
In this publication, a causal link between Pyridostigmine Bromide (currently contained in a variety of countermeasure stockpiles) and the human condition known as Gulf War Syndrome (GWS) was established.
It is important to understand that Galantamine is in a totally different class of AChE inhibitor compounds than is Pyridostigmine Bromide and does not have the potential for similar sequelae.