Science2018-09-13T22:34:30+00:00

Science

Overview of Botulinum Neurotoxins

Botulinum neurotoxins are naturally occurring molecules produced by Clostridium botulinum. Botulinum neurotoxins function as muscle relaxants, blocking muscle hyperactivity by preventing acetylcholine release, a neurotransmitter that is essential for muscle contraction, from nerve cells.

Most approved botulinum neurotoxin products are derived from botulinum neurotoxin serotype A (BoNT/A). Regulatory approvals expanded the range of applications of botulinum neurotoxins to include cervical dystonia and various conditions associated with muscle spasms as well as aesthetic applications to achieve desired outcomes. Commercially available botulinum neurotoxins have been an attractive therapeutic treatment modality with a favorable safety profile.

While these products have been effective, in the absence of other treatment alternatives, they have certain limitations.  They have the disadvantage of a slow onset of efficacy that typically takes approximately three to seven days. In addition, the long duration of action of these products leads to long-term muscle immobilization, which can result in muscle atrophy and muscle weakness.  These attributes are not ideal for acute indications that require faster rehabilitation, quick reduction of musculoskeletal pain, and faster recovery of normal function.

Botulinum neurotoxin serotype E

Botulinum neurotoxin serotype E (BoNT/E) acts through a similar mechanism as BoNT/A with two key differences: a faster onset of efficacy and a shorter duration of activity based preclinical and clinical data, which we believe will provide BoNT/E with product opportunities beyond those available to BoNT/A.

BoNT/A and BoNT/E both cleave SNAP-25, a protein found on the inner surface of the nerve cell membrane that is essential for docking of acetylcholine containing synaptic vesicles. Cleavage of SNAP-25 prevents synaptic vesicle docking, thereby preventing acetylcholine release and subsequent muscle contraction.