BOTOX® is an important medicine that over the last 15 years of clinical use has helped millions of patients with serious medical conditions worldwide. Pharmaceutical manufacturers using Clostridium botulinum toxin (BOTOX®) in drugs are required by the Food and Drug Administration (FDA) in the United States and by other worldwide health regulatory agencies to protect patients and consumers by assuring product safety and efficacy through animal testing and other methods.
Roche's xCELLigence System Designed to Reduce Animal Testing in Pharmaceutical Development
In a recent study (Biochemica 4/2008, in print), James O´Connell et.al. from ACEA Biosciences in San Diego have used the label-free, real time xCELLigence cell analyzer system to test biological effects of botulinum toxin on live cells. Currently, there is no in vitro
assay approved by the USFDA and other international regulatory bodies for the release of Botulinum Toxin A. The preliminary results indicated that the xCELLigence System was able to detect specific biological effects on two CNS-derived cell lines - A172 glioblastoma cell line and SH-SY5Y neuroblastoma cell line. Additional cell lines are currently being evaluated.
According to Dr. O’Connell, the xCELLigence System was also used to identify closely related Clostidrium difficile
toxins A and B directly from stool samples using cell culture and specific toxin neutralization with highly specific toxin A and B antibodies. “The test as performed with the xCELLigence System is extremely sensitive and is highly specific. Our preliminary results with botulinum toxin indicate the possibility of replacing the animal test for BOTOX®
with a highly sensitive and specific real time, label free cell-based assay on xCELLigence.”
“We believe that the combination of the xCELLligence System with other high information content systems such as the 454 and Roche NimbleGen Systems will bring a new level of accuracy and information to in vitro
testing that will significantly reduce the number of animal tests required in pharmaceutical development,” comments James O’Connell.
In the U.S., BOTOX®
(botulinum toxin type A, Allergan, Inc.) is approved for the treatment of four debilitating conditions, including two eye disorders that can lead to functional blindness, cervical dystonia which is a painful movement disorder affecting the head and neck, and excessive underarm sweating. Worldwide, it is approved for twenty different indications in more than seventy-five countries, and the therapeutic use of BOTOX®
accounts for the majority of all BOTOX®
The safety and efficacy of BOTOX®
currently is assessed by using the LD50 Test (Lethal Dose 50%). The LD50 Test involves injecting groups of animals with different doses of a chemical to estimate the dose that kills 50% of them. In the case of BOTOX®
, mice are injected with the active ingredient—a form of the same toxin that causes Botulism food poisoning—and the mice experience differing levels of muscular paralysis.
For more information on the technology, please visit the article webpage.
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