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Review
. 2018 May 18;10(5):208.
doi: 10.3390/toxins10050208.

The Expanding Therapeutic Utility of Botulinum Neurotoxins

Elena Fonfria  1 , Jacquie Maignel  2 , Stephane Lezmi  3 , Vincent Martin  4 , Andrew Splevins  5 , Saif Shubber  6 , Mikhail Kalinichev  7 , Keith Foster  8 , Philippe Picaut  9 , Johannes Krupp  10
Affiliations
Review

The Expanding Therapeutic Utility of Botulinum Neurotoxins

Elena Fonfria et al. Toxins (Basel). .

Abstract

Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present an overview of the current therapeutic landscape and explore the diversity of BoNT proteins as future therapeutics. In recent years, novel indications have emerged in the fields of pain, migraine, overactive bladder, osteoarthritis, and wound healing. The study of biological effects distal to the injection site could provide future opportunities for disease-tailored BoNT therapies. However, there are some challenges in the pharmaceutical development of BoNTs, such as liquid and slow-release BoNT formulations; and, transdermal, transurothelial, and transepithelial delivery. Innovative approaches in the areas of formulation and delivery, together with highly sensitive analytical tools, will be key for the success of next generation BoNT clinical products.

Keywords: delivery; formulation; new indications.

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Conflict of interest statement

All authors are Ipsen employees.

Figures

Figure 1
Figure 1
Whatever the mouse strain, BoNT/B1 is significantly more potent than BoNT/A1 in a model of detrusor contractions (A,C), while the potencies of BoNT/A1 and BoNT/B1 were equal in the phrenic nerve-hemidiaphragm preparation (B,D).* p < 0.05 (unpaired Student’s t test) [89].
Figure 2
Figure 2
Immunohistochemistry staining of cleaved SNAP25 in rat lumbar spinal cord after BoNT/A injection in the left gastrocnemius muscle. Intense staining was found in the ipsilateral ventral horn neuropil, and only traces were found in the contralateral side (SL, VM, unpublished data).
Figure 3
Figure 3
Immunohistochemistry staining of cleaved SNAP25 in rat muscle injected with BoNT/A (SL, VM, unpublished data).
See this image and copyright information in PMC

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