Following the demonstration of safety in Phase I extended dosing studies, Phase II studies are expected to begin for the treatment of sudden cardiac arrest and ischemic stroke.

Cardiac arrest (SCA) claims up to 450,000 lives annually in the United States and accounts for up to 20% of all deaths in the US. The survival rate for out-of-hospital SCA is about 5%, primarily because hypoxic brain injury begins about four minutes after arrest, with brain death occurring around twelve minutes post-arrest. Time to defibrillation (electrically) is currently the key to increasing survival, and major healthcare changes are underway to achieve this. Automated external defibrillators (AEDs) are increasingly being placed with first responders (EMTs, police, fire fighters, etc.), in airports and shopping malls, and other public places. After minimal training, sixth-grade students’ performance with AEDs in mock arrest situations was comparable to that of cardiologists! In cities such as New York, where average response times to defibrillation are 12 minutes, the survival rate is about 5%; in Seattle, where average response time is 7 minutes, survival is 30%; and, in Rochester, Minnesota, where average response time is 6 minutes, survival is 45%.

It seems clear that administration of a neuronal protective agent such as Neu2000 might also change the paradigm of survival for this condition, where mere minutes of hypoxic injury make the difference between life and death. Many of the same mechanisms that mediate neuronal cell death following ischemic stroke are active following cardiac arrest. By reducing the toxicity of glutamate, oxygen free radicals and zinc, Neu2000 could have a significant impact on survival improvement or neurological outcomes following cardiac arrest.

Stroke

Neu2000 was initially discovered as a treatment for ischemic stroke, which remains the primary focus of the drug’s development. Neu2000’s strong anti-oxidation activity, its potent NMDA antagonist activity, and its anti-zinc protective activity make it a promising neuroprotectant to treat ischemic stroke. Many previous drug candidates, particularly ion channel blockers, have suffered from the need to administer drug within as early as three hours of a stroke event in order to show clinical trends of efficacy. This is possibly due to the fact that their single mechanism of action addresses only an early toxicity. The three mechanisms addressed by Neu2000, on the other hand, address toxicities found both early and later in the stroke injury process. Glutamate excitotoxicity, for example, can only be ameliorated in animal models by administration of NMDA-antagonist drugs during the first few hours following anoxic injury. Damage from oxygen free radicals, on the other hand, can be reduced by antioxidant treatments commencing as late as 24 hours after anoxic injury, depending upon the model. Neu2000’s multi-mechanism qualities, however, allow its use to mitigate both early and late phase toxicities of anoxia. Importantly, Neu2000 is both blood/brain barrier and membrane permeable, in contrast to several drugs that have recently failed during human clinical studies.

The annual incidence of ischemic stroke in the United States is about 600,000. It is the leading cause of serious, long-term disability in the United States, resulting in $53 billion of annual direct and indirect costs. The mean lifetime cost per patient is estimated at $140,000, with 30-day costs running from $13,000 for a mild ischemic stroke to $20,000 for a severe stroke.

 

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