AbobotulinumtoxinA: A 25-Year History

Abstract

During the late 1960s and early 1970s, Alan Scott showed that intramuscular injections of botulinum toxin (BoNT) corrected nonaccommodative strabismus without resorting to surgery. The UK doctors who trained with Scott soon realized the significant potential offered by BoNT type A as a therapeutic option for several difficult-to-treat diseases. This led to a collaboration between these pioneering clinicians and the Centre for Applied Microbiology and Research at Porton Down, United Kingdom, and, in turn, to the development and commercialization of abobotulinumtoxinA as Dysport (Dystonia/Porton Down; Ipsen Biopharm Ltd., Wrexham, UK). Dysport was approved in Europe for the treatment of specific dystonias in December 1990 and now has marketing authorizations in 75 countries. Since then, the use of BoNT in therapeutic and aesthetic indications has grown year-on-year, and continues to expand well beyond Scott’s initial aim. For example, ongoing trials are assessing potential new indications for BoNT-A, including acne and psoriasis. Furthermore, a growing number of other BoNT products, often termed “biosimilars,” together with innovative formulations of well-established BoNT types, are likely to reach the market over the next few years. This review focuses on the history of Dysport to mark the 25th anniversary of its first launch in the United Kingdom.

Paravertebral injection of botulinum toxin‐A reduces lumbar vertebral bone quality

“…To this end, we created a rat model of paravertebral muscle atrophy by locally injecting BTX a zinc‐dependent endopeptidase neurotoxin that specifically targets the neuromuscular junction . Previous studies have shown that focal intramuscular injection of BTX effectively denervates muscles by inhibiting the release of acetylcholine at the neuromuscular junction, resulting in local paresis and atrophy of the targeted muscle . Thus, BTX is used clinically to manage skeletal muscle spasticity associated with cerebral palsy, as well as other neuromuscular diseases .…”

“…Previous studies have shown that focal intramuscular injection of BTX effectively denervates muscles by inhibiting the release of acetylcholine at the neuromuscular junction, resulting in local paresis and atrophy of the targeted muscle . Thus, BTX is used clinically to manage skeletal muscle spasticity associated with cerebral palsy, as well as other neuromuscular diseases . It attenuates the forceful contractions generated by patients with cerebral palsy, thus decreasing the strength of the spastic response.…”

“…We hypothesized that a reduction in mechanical stimulation of the paravertebral muscles following resection or injection of botulinum toxin‐A would lead to bone loss in the adjacent axial skeleton. Botulinum toxin‐A is a zinc‐dependent endopeptidase neurotoxin that specifically targets the neuromuscular junction, inhibiting the release of acetylcholine at the neuromuscular junction, and resulting in local paresis and atrophy of the targeted muscle . We used ovariectomized and sham‐treated rats as positive and negative controls, respectively, to distinguish the effects of muscle atrophy from the effects of hormone deficiency.…”

Characterization of clostridium botulinum neurotoxin serotype A (BoNT/A) and fibroblast growth factor receptor interactions using a novel receptor dimerization assay

“…Botulinum Neurotoxin Type A (BoNT/A) is a 150 kDa metalloenzyme belonging to the family of neurotoxins produced by Clostridium botulinum which causes temporary muscle paralysis by inhibiting acetylcholine release at the neuromuscular junction [1-4]. The neuronal specificity and high potency of BoNT/A has allowed its use in the treatment of a large number of medical and aesthetic conditions [3, 5-7], relying on injection of picomolar (pM) concentrations of the toxin. Though BoNT/A has been the subject of extensive study, greater understanding of the complex mechanism associated with BoNT/A’s neuronal specificity and cellular entry could lead to further therapeutic applications.…”

Introduction to the Supplement: A Review of AbobotulinumtoxinA (Dysport)

“…8 The paper begins with the reports of outbreaks of botulism from back in the late 1700s and continues to the first publications describing botulism in the 1800s, then focusing on the 25-years since Dysport was launched in the United Kingdom. Examining the 25-year history of ABO provides us with a clearer picture of where the product came from and opens up novel lines of inquiry for future use.…”