Re-Engineering Clostridial Neurotoxins for the Treatment of Chronic Pain

Pickett, Andy

doi:10.2165/11534510-000000000-00000

Cited by 21 publications

(16 citation statements)

References 85 publications

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“…The established ability to produce neurotoxins by recombinant protein expression (Bade et al, 2004; Band et al, 2010; Masuyer et al, 2014, 2015) and to modify them to create engineered neurotoxins with enhanced specificity for nociceptive nerve terminals will expand the therapeutic utility of BoNT for pain treatment. In this context, an innovative class of biopharmaceuticals obtained by replacing the native binding domain with another protein to redirect the light chain to a different nerve or cell has been recently proposed (Chaddock et al, 2004; Pickett, 2010; Masuyer et al, 2014). …”

Section: Pharmacologymentioning

confidence: 99%

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

et al. 2017

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The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.

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Section: Pharmacologymentioning

confidence: 99%

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

et al. 2017

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“…This may be achieved by replacing the native binding domain with another protein to re-direct the light chain to a different nerve or cell [119]. Such modifications may enable BoNTs to treat pain without engendering weakness of nearby muscles.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Botulinum Neurotoxin for Pain Management: Insights from Animal Models

Pavone¹,

Luvisetto²

2010

Toxins

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The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.

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“…Additional sources of pain in which BoNT-A has been shown to be useful are diabetic polyneuropathy, trigeminal neuralgia, chronic back and shoulder pain, myofascial pain, temporomandibular joint disorders, and pain due to arthritis and multiple sclerosis. 90-92 …”

Section: Medical Developmentsmentioning

confidence: 99%

“…93 Inhibition of acetylcholine signaling in the NMJ is also known to inhibit the release of neurotransmitters such as substance P, glutamate, and calcitonin gene-related peptide, which also serves to dull the sensation of pain. 90 …”

Section: Medical Developmentsmentioning

confidence: 99%

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New Uses of AbobotulinumtoxinA in Aesthetics

Schlessinger¹,

Gilbert²,

Cohen³

et al. 2017

Aesthetic Surgery Journal

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BotulinumtoxinA (BoNT-A) is now widely established for the main approved indication of reducing glabellar lines, and is also widely used off-label to improve the appearance of wrinkles and lines in other parts of the face. The number of aesthetic procedures continues to increase as the patient population becomes more diverse, in particular with increasing numbers of people of color and men. Further developments in treatment may continue to expand the audience for BoNT-A by making procedures more comfortable and by delivering a more natural, less static appearance. These may be achieved through use of combinations of BoNT-A with other aesthetic procedures, tailoring the dose of toxin to the patient’s muscle mass or by using novel injection and application techniques. Beyond amelioration of facial lines, encouraging results have been seen with the use of BoNT-A to improve the appearance of hypertrophic and keloid scars and even to prevent them. Studies have been conducted with scars in various parts of the body and further research is ongoing. Dermatological and other medical uses for BoNT-A are also active areas of research. Injections of BoNT-A have been shown to reduce signs and symptoms of acne, rosacea, and psoriasis, to reduce neuromuscular pain, and to bring about significant improvements in a number of rare diseases that are caused or exacerbated by hyperhidrosis. This paper reviews these new uses for BoNT-A, looking at the rationale for their use and discussing the results of published case studies and clinical trials. These areas have shown great promise to date, but more and larger clinical studies will be required before these treatments become a clinical reality. To this end details are also provided of clinical trials currently listed in the main clinical trials database to highlight research areas of particular interest.

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Re-Engineering Clostridial Neurotoxins for the Treatment of Chronic Pain

Cited by 21 publications

References 85 publications

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

Botulinum Neurotoxin for Pain Management: Insights from Animal Models

New Uses of AbobotulinumtoxinA in Aesthetics

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