What was the evolution of therapeutic botulinum toxin (BoNT)?

Updated: Jul 13, 2018
  • Author: Divakara Kedlaya, MBBS; Chief Editor: Elizabeth A Moberg-Wolff, MD  more...
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Answer

Answer

The German physician and poet Justinus Kerner (1786-1862) first developed the idea of a possible therapeutic use of botulinum toxin, which he called "sausage poison." [2]

  • In 1870, Muller (another German physician) coined the name botulism. The Latin form is botulus, which means sausage.

  • In 1895, Professor Emile Van Ermengem, of Belgium, first isolated the bacterium Clostridium botulinum.

  • In 1928, Dr. Herman Sommer, at the University of California, San Francisco, first isolated in purified form botulinum toxin type A (BoNT-A) as a stable acid precipitate.

  • In 1946, Dr. Edward J Schantz succeeded in purifying BoNT-A in crystalline form–cultured Clostridium botulinum and isolated the toxin.

  • In 1949, Dr. Burgen's ASV group discovered that botulinum toxin blocks neuromuscular transmission.

  • In the 1950s, Dr. Vernon Brooks discovered that when BoNT-A is injected into a hyperactive muscle, it blocks the release of acetylcholine from motor nerve endings.

  • In 1973, Dr. Alan B. Scott, of Smith-Kettlewell Eye Research Institute, used BoNT-A in monkey experiments; in 1980, he used BoNT-A for the first time in humans to treat strabismus.

  • In December 1989, BoNT-A (BOTOX®) was approved by the US Food and Drug Administration (US FDA) for the treatment of strabismus, blepharospasm, and hemifacial spasm in patients aged younger than 12 years.

  • On December 21, 2000, BoNT-A received US FDA approval for treatment of cervical dystonia.

  • In 2001, the United Kingdom approved BOTOX®, synthesized by Allergan, for axillary hyperhidrosis (excessive sweating). Canada approved BOTOX® for axillary hyperhidrosis, focal muscle spasticity, and cosmetic treatment of wrinkles at the brow line.

  • On April 15, 2002, the US FDA announced the approval of BOTOX® Cosmetic to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines). On July 21, 2011, the US FDA approved incobotulinumtoxinA (Xeomin) for temporary improvement in the appearance of moderate-to-severe glabellar lines, or frown lines between the eyebrows, in adult patients.

  • In July 2004, the US FDA approved BOTOX® to treat severe underarm sweating, known as primary axillary hyperhidrosis that cannot be managed by topical agents, such as prescription antiperspirants.

  • The acceptance of BoNT-A use for the treatment of different chronic pain disorders is growing. However, it has not been approved by the US FDA for any chronic pain conditions except for chronic migraine.

  • The clinical use of BoNT-B has been studied, and several products currently are available commercially (eg, MyoBloc, in the United States; NeuroBloc, in Europe). MyoBloc was approved by the US FDA on December 8, 2000, for treatment of cervical dystonia, to reduce the severity of abnormal head position and neck pain.

  • Use of BoNT-F also is under investigation in patients who have become immunologically resistant to serotypes A and B.

  • On April 29, 2009, abobotulinumtoxinA (Dysport) was approved by the US FDA for the treatment of adults with cervical dystonia to reduce the severity of abnormal head position and neck pain in both toxin-naïve and previously treated patients.

  • On March 9, 2010, the US FDA approved onabotulinumtoxinA (BOTOX®) to treat spasticity in the flexor muscles of the elbow, wrist, and fingers in adults with stroke, traumatic brain injury, or the progression of multiple sclerosis.

  • On August 2, 2010, the US FDA announced the approval of incobotulinumtoxinA (Xeomin®) for the treatment of adults with cervical dystonia, to decrease the severity of abnormal head position and neck pain in both botulinum toxin-naïve and previously treated patients and for blepharospasm in adults previously treated with BOTOX®.

  • On October 15, 2010, the US FDA approved onabotulinumtoxinA (BOTOX®) injection to prevent headaches in adult patients with chronic migraine. Chronic migraine is defined as having a history of migraine and experiencing a headache on most days of the month.

  • On August 24, 2011, the US FDA approved onabotulinumtoxinA (BOTOX®) injection for the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (eg, spinal cord injury, multiple sclerosis) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

  • On September 11, 2013, the US FDA approved onabotulinumtoxinA (BOTOX®) for the temporary improvement in the appearance of moderate to severe lateral canthal lines, known as crow’s feet. This is the only FDA-approved drug treatment option for lateral canthal lines.

  • On July 16, 2015, the US FDA approved Dysport® (abobotulinumtoxinA) for the treatment of upper limb spasticity (ULS) in adult patients to decrease the severity of increased muscle tone in elbow flexors, wrist flexors and finger flexors.

  • On December 23, 2015, the US FDA approved Xeomin® (incobotulinumtoxinA) for the treatment of upper limb spasticity (ULS) in adult patients.


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