SAN DIEGO--(BUSINESS WIRE)--Jan. 9, 2003-- Applied Molecular Evolution, Inc. (AME) (Nasdaq:AMEV - News) today announced that it has demonstrated protection from lethal cocaine overdose in a preclinical study of an optimized form of Butyrylcholinesterase (BChE), a naturally occurring human serum enzyme that catalyzes the hydrolysis, or breakdown, of cocaine in the bloodstream. The AMEsystem(TM) was utilized to engineer AME-359, a new molecule having greater than 250-fold improvement in potency over the wild-type enzyme as demonstrated by AME in an animal model system.
"AMEsystem(TM) technology was leveraged with financial support from the National Institutes of Health to demonstrate proof-of-concept that AME can potentially create new, important therapeutics from natural proteins that exist in the human body. Although BChE is able to hydrolyze cocaine, its extremely slow rate of action makes it unlikely to have therapeutic efficacy at reasonable doses. Our engineering has created a similar but novel molecule that may have potential as a treatment for cocaine overdose," commented William D. Huse, M.D., Ph.D., President, CEO and Chairman of AME. "AME-359 may potentially address the unmet medical need of acute cocaine overdose by accelerating the clearance of cocaine from the bloodstream. AME-359 therefore represents an entirely new approach to treating a critical condition with serious medical and socioeconomic consequences."
In the animal model, rats were infused with two mg/kg per minute of cocaine for up to 15 minutes. Without treatment, 100% of the rats died in approximately 12 minutes. Treatment with doses up to 50 mg/kg of wild-type BChE provided no protection from lethality. By contrast, AME-359 provided 50% survival at 0.2 mg/kg and 100% survival at 0.5 mg/kg demonstrating complete protection from the lethal cocaine overdose. These results suggest that AME has engineered improvements in BChE's catalytic rate that improve the enzyme's ability to neutralize the toxic effects of cocaine in vivo by greater than 250-fold. |
