Neurons from stem cells could replace mice in botulinum test

Feb 06, 2012

(PhysOrg.com) -- Using lab-grown human neurons, researchers from the University of Wisconsin-Madison have devised an effective assay for detecting botulinum neurotoxin, the agent widely used to cosmetically smooth the wrinkles of age and, increasingly, for an array of medical disorders ranging from muscle spasticity to loss of bladder control.

The new assay uses neurons, the critical impulse conducting cells of the , derived from induced . It is the first test to employ stem cell derivatives to reliably and quantitatively detect and the antibodies that can neutralize the toxin's effects.

The assay is likely to draw considerable interest from industry as a potential replacement for the mouse, an animal now used by the thousands to control the potency of pharmaceutical preparations of the powerful neurotoxin.

Using cells provided by Madison-based Cellular Dynamics International, a company that industrially manufactures induced pluripotent and their derivative for use in research and industry, the University of Wisconsin-Madison team devised an assay that is more sensitive than the mouse assay required for quality control of pharmaceutical preparations of botulinum toxin.

"This is an optimal testing platform for botulinum neurotoxin products," explains Sabine Pellett who, with UW-Madison professor of bacteriology Eric A. Johnson, led the new study published this week in the journal Toxicological Sciences. "A cell-based assay that is at least as sensitive and reproducible as the mouse bioassay can serve as a viable alternative and largely eliminate the need to use animals."

The toxin is used most famously for cosmetic purposes to erase the that come with age. However, it is also used in a growing number of medical applications. Since it was first approved in 1990 for use in human patients with or cross-eye, the toxin, which works by blocking communication between nerves and muscles, has been used to successfully treat excessive sweating, chronic migraine headaches, painful neck spasms known as dystonia, and muscle conditions associated with cerebral palsy, multiple sclerosis and stroke. In 2010, the Food and Drug Administration (FDA) approved the toxin for use in treating loss of bladder control. Pharmaceutical applications of the toxin underpin a market that easily exceeds $1 billion annually.

Botulinum toxin is a protein produced by the bacterium Clostridium botulinum. It is the most potent toxin known to science and before its first experimental medical application to treat cross-eye was best known as a food poison. The methods to produce the toxin in large quantities and to precise specifications were pioneered at UW-Madison by Johnson and his late mentor, Ed Schantz.

Because of its incredible potency, the quality and dosages of the toxin for medical use must be carefully prepared.

The preparations made by pharmaceutical companies, says Johnson, actually contain very little toxin. To ensure that batches of the agent are of the correct therapeutic dose and of uniform quality, they are tested by injecting mice at a specified dosage that kills half of all mice exposed to the toxin.

"The mouse assay has many drawbacks and hundreds of thousands of mice are used for this every year," Pellett explains. "The most important result of this study is the high sensitivity of the assay, greater than the mouse bioassay, which is required for quality control."

The pharmaceutical industry, Johnson adds, is under pressure from the FDA to develop alternatives to the mouse. One cell-based assay has already been developed by Allergan, the company that makes BOTOX, the most famous trade name for . However, the details of that assay have not been made available.

"The assay we developed is another cell based assay," notes Pellett, "one that uses normal human neurons derived from induced , and which can be optimized for any pharmaceutical botulinum neurotoxin product."

Explore further: Genetics link found in search for sweet strawberries

More information: toxsci.oxfordjournals.org/

Related Stories

New insights about Botulinum toxin A

Dec 02, 2010

A new study by researchers at the Faculty of Kinesiology, University of Calgary, is raising questions about the therapeutic use of botulinum toxin A.

Foodborne Staph Toxin Pinpointed by New Assay

Dec 15, 2009

(PhysOrg.com) -- Most people need about two days to recover from being sickened by foods contaminated with what's known as staphylococcal enterotoxin A, or "SEA." Produced by Staphylococcus aureus bacteria, ...

Recommended for you

Deadly human pathogen Cryptococcus fully sequenced

9 hours ago

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...

Building better soybeans for a hot, dry, hungry world

Apr 16, 2014

(Phys.org) —A new study shows that soybean plants can be redesigned to increase crop yields while requiring less water and helping to offset greenhouse gas warming. The study is the first to demonstrate ...

User comments : 0

More news stories

Deadly human pathogen Cryptococcus fully sequenced

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...

Chronic inflammation linked to 'high-grade' prostate cancer

Men who show signs of chronic inflammation in non-cancerous prostate tissue may have nearly twice the risk of actually having prostate cancer than those with no inflammation, according to results of a new study led by researchers ...