Botulinum Toxin : Use as Medicine

by Food and Drug Administration (FDA)

(Page 3 of 3)

Meanwhile, purified botulism toxin is the first bacterial toxin to be used as a medicine. FDA licensed botulinum toxin as Oculinum in December 1989 for treating two eye conditions — blepharospasm and strabismus — characterized by excessive muscle contractions. It is now marketed under the trade name Botox.

Small doses of the toxin are injected into the affected muscles. As happens with botulism, the toxin binds to the nerve endings, blocking the release of the chemical acetylcholine, which would otherwise signal the muscle to contract. The toxin thus paralyzes or weakens the injected muscle but leaves the other muscles unaffected. The injections "block extra contraction [of the muscle] but leave enough strength for normal use," says Barbara Karp, M.D., deputy clinical director of the National Institutes of Health's National Institute of Neurological Disorders and Stroke.

The effect of Botox is shown in the above photos. At left, a patient with blepharospasm before injection with Botox is unable to open her eyes due to abnormal muscle contractions. At center, still pre-injection, she uses her fingers to keep her eyes open. At right, after injection, her eyes stay open without difficulty. (Photos courtesy Joseph Jankovic, M.D., professor of neurology, Baylor College of Medicine, Houston, Texas)

Although the two eye conditions are the only indications for which it is licensed, botulinum toxin has been used investigationally for a variety of other conditions. "The main disease [group] the toxin is being used for is dystonias — neurologic diseases involving abnormal muscle posture and tension," Karp says. Examples include spasmodic torticollis (contractions of the neck and shoulder muscles), oral mandibular dystonia (clenching of the jaw muscles), and writers' and musicians' cramps.

Other investigational uses include: spasmodic dysphonia (which results in speech that is difficult to understand), urinary bladder muscle relaxation (such as in cases where muscle contraction is severe enough to require catheterized urination), esophageal sphincter muscle relaxation, and the management of tics.

Experience shows that "it works better for some things than others," NIH's Karp says. For example, "it works better for disorders that involve small muscles than large muscles," she says. But for about 2 to 5 percent of patients, the injections simply don't work at all, she adds.

Injections usually have to be repeated, as the effects usually only last about three to four months, although sometimes they can last over a year. Because of this, up to 10 percent of patients eventually develop antibodies to the toxin; this is more likely in patients who receive higher doses at more frequent intervals. Therefore, the makers of the biologic recommend that its dosage be kept as low as possible.

There are seven different types of botulinum toxin, and the currently marketed therapeutic toxin is type A. NIH is studying whether patients who have become immune to injections of type A toxin can successfully be treated by toxins of other types. So far, the research indicates that using type F to treat people with antibodies to type A seems to work, Karp says.

Botulinum toxin has "an amazing safety record," says Bill Habig, Ph.D., the recently retired deputy director of FDA's division of bacterial products in the Center for Biologics Evaluation and Research. "Considering it's one of the most toxic materials known and there was a lot of concern about it, it's turned out to be very safe," he says.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.