Toxin Drugs - A History

BtxA type drugs have had a long, interesting and still-evolving story.

The 1820s


No one really understood the biological basis for food poisoning until Dr. Justinus Kerner began to study a batch of improperly prepared blood sausages responsible for the death of several dozen Germans. Kerner posited that there was something in the spoiled sausages that brought on the disease, something he called “wurstgift” (German for sausage poison).

His experiments (including injecting himself) and case studies led to a better understanding of the neurological symptoms of food-borne botulism (drooping eyelids, difficulty swallowing, muscle weakness, and if left untreated, paralysis and respiratory failure).  He also offered up suggestions for treatment and prevention of food poisoning, and paved the way for today’s therapeutic use of the toxin.  He also coined the name botulism (from the latin botulus meaning “sausage”).

The 1890s


Dr. Emile Pierre van Ermengem of Belgium was asked to investigate an outbreak of botulism following a funeral dinner where three people died and 23 were paralyzed (a bad ham).

Van Ermengem,  was able to make a connection between botulism and a spore-forming bacterium he named Bacillus botulinus (it was later renamed Clostridium botulinum). Seven strains of botulinum toxin were eventually identified (A through G); four of them (A, B, E and F) would be shown to cause illness in humans.

The 1940's


With the outbreak of World War II, the U.S. began researching biological weapons, including botulinum toxin (the nerve toxin produced by Clostridium botulinum), considered to be deadliest substance in the world. One plan, according to a 2004 article in Clinical Medicine (The Journal of the Royal College of Physicians of London), was to have Chinese prostitutes slip tiny toxic pills into the food and/or drink of high-ranking Japanese officers. According to the authors, a batch of gelatin capsules filled with botulinum toxin was produced, but the project was abandoned before the poison pills could be put into action.

1949

Arnold Burgen discovered through experimentation that botulinum toxin blocks neuromuscular transmission through decreased acetylcholine (acts as neurotransmitter) release.

The '50s and ’60s


Dr. Edward J. Schantz and his colleagues were able to purify botulinum toxin type A into crystalline form. In 1953, physiologist Dr. Vernon Brooks discovered that injecting small amounts into a hyperactive muscle blocked the release of acetylcholine from motor nerve endings, causing temporary “relaxation.”

In the 1960s, ophthalmologist Dr. Alan B. Scott started injecting botulinum toxin type A into monkeys, theorizing its muscle-relaxing effects might help in the treatment of crossed eyes (or strabismus). Before long, botulinum toxin type A became the go-to toxin in research labs around the world (despite fears about its use in “germ warfare”).

The '70s and ’80s


In 1978, Scott received FDA approval to inject tiny amounts of botulinum toxin into human volunteers and soon, the results started rolling in. In the early 1980s, the eye doctor published a number of studies including a 1981 paper in the Transactions of the American Ophthalmological Society that asserted botulinum toxin “appears to be a safe and useful therapy for strabismus.” Additional research showed the drug’s benefits went beyond ophthalmology, providing patients with temporary relief from facial spasms, neck and shoulder spasms, even vocal cord spasms. In 1988, drugmaker Allergan acquired the rights to distribute Scott’s batch of botulinum toxin type A (or Oculinum, as it was then known) and a year later, the FDA approved botulinum toxin type A for the treatment of both strabismus and blepharospasm (spasms of the eyelid muscle). Shortly thereafter, Allergan acquired Scott’s company and changed the drug’s name to the compact, catchy “Botox.”

The 1990s


As research continued, other potential uses came to light. Bladder spasms, excessive sweating, even cerebral palsy in children all were alleviated — at least for a short time — by injections of the neurotoxin. But by far the most earth-shattering discovery came about by accident when Canadian ophthalmologist Dr. Jean Carruthers noticed her blepharospasm patients were starting to lose their frown lines. In 1992, she and her dermatologist husband published a study in the Journal of Dermatologic Surgery and Oncology stating that though temporary, “treatment with C. botulinum-A exotoxin is a simple, safe procedure” for the treatment of brow wrinkles. Dermatologistsimmediately took note (and took advantage of this “off-label” use) and by 1997, Botox use spiked so high the country’s supply temporary ran out, causing panic among its devotees and prompting the New York Times to announce “Drought Over, Botox Is Back” once a new batch received FDA approval.

2000

Botox got the FDA’s approval for the treatment of cervical dystonia (neck and shoulder spasms);

2002

Botox Cosmetic (the frown-line fixer) got its official government go-ahead, greenlighting Allergan to begin a multi-million-dollar marketing campaign to boost its already healthy Botox sales, which had reached $310 million by the end of 2001.

2003

The drug had been profiled in nearly 14,000 TV and print stories (in the U.S. alone), end-of-year sales had reached nearly $440 million and Allergan had proclaimed Botox Cosmetic one of the most successful pharmaceutical brand launches in the company’s 53-year-history.

2004

Allergan received yet another FDA approval, this time for the treatment of severe underarm sweating (hyperhidrosis).

2006

Botox sales had soared past the $1 billion mark, with cosmetic uses accounting for about half of sales.

2009

Marked the 20th Anniversary of Botox.

2010

In 2010 the FDA approved Botox ® therapy to treat increased muscle stiffness for upper limb spasticity. Botox ® was studied to treat the prevention of recurring headaches in adults diagnosed with chronic migraines, and approved by the FDA.

2013

Allegan's sales amounted to almost $2 billion.