Abstract
Background: Two decades ago, botulinum neurotoxin (BoNT) type A was introduced to the commercial market. Subsequently, the toxin was approved by the FDA to address several neurological syndromes, involving muscle, nerve, and gland hyperactivity. These syndromes have typically been associated with abnormalities in cholinergic transmission. Despite the multiplicity of botulinal serotypes (designated as types A through G), therapeutic preparations are currently only available for BoNT types A and B. However, other BoNT serotypes are under study for possible clinical use and new clinical indications; Objective: To review the current research on botulinum neurotoxin serotypes A-G, and to analyze potential applications within basic science and clinical settings; Conclusions: The increasing understanding of botulinal neurotoxin pathophysiology, including the neurotoxin’s effects on specific neuronal populations, will help us in tailoring treatments for specific diagnoses, symptoms and patients. Scientists and clinicians should be aware of the full range of available data involving neurotoxin subtypes A-G.
Highlights
Over the past three decades, there has been a continuing fascination with botulinum neurotoxin (BoNT) and the opportunities for use of this potentially deadly neurotoxin as a treatment in certain clinical settings
The toxin produced by Clostridium Tetani (TeTx) presents similar structures and mechanisms of action compared with botulinum neurotoxin, and it is synthesized as a single-chain protein of ~150 kDa which is proteolytically activated to di-chain derivatives involving a light chain (Lc) of ~50 kDa, linked by a single disulfide bridge to a heavy chain (Hc) of
BoNT types C, D, E and F are attached in M complexes, L complexes are 450–500 kDa, consisting of M complexes associated with non-toxic haemagglutinin proteins (HP)
Summary
Over the past three decades, there has been a continuing fascination with botulinum neurotoxin (BoNT) and the opportunities for use of this potentially deadly neurotoxin as a treatment in certain clinical settings. BoNT is used primarily as a focal injectable treatment, resulting in fewer side effects than systemically administered medications, it has evolved to become the preferred treatment of choice for management of many forms of dystonia, limb spasticity, cosmetic glabellar lines, hyperhidrosis, and sialorrhea [1]. BoNT has a broad spectrum of off-label indications, including focal hand dystonia, lower limb spasticity [6,7], management of chronic anal fissures [4], and tension headaches [8]. The commercially available neurotoxins include three main brands of BoNT/A: OnabotulinumtoxinA (BOTOX®), AbobotulinumtoxinA (DYSPORT®), IncobotulinumtoxinA (XEOMIN®), and a brand of BoNT type B, RimabotulinumtoxinB (MYOBLOC® or NEUROBLOC®) [9]. This review will cover the clinical scope, including mechanisms of action, and will summarize the neurotoxin properties of the seven different toxin serotypes (A-G). We will discuss the potential opportunities for utilizing the various serotypes in clinical settings
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