Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models

Franz, Colin K.; Puritz, Alyssa; Jordan, Lewis A.; Chow, Jeffrey; Ortega, Joaquı́n M.; Kiskinis, Evangelos; Heckman, C. J.

doi:10.1177/1545968318790020

Cited by 13 publications

(13 citation statements)

References 49 publications

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“…However, if chemodenervation by BoNT/A is able to serve as a nonsurgical alternative for the conditioning lesion, it may be possible to exploit this phenomenon for achieving accelerated nerve growth and presumably a more satisfactory outcome after nerve injury and repair. Data consistent with this expectation were recently provided by Franz et al [ 139 ]. The authors injected 0.25 units of BoNT/A (onabotulinumtoxinA, Botox ® ) unilaterally into the triceps surae muscle group in mice.…”

Section: Attributes Of Bont/a That Make a Promising Therapeutic Agent...supporting

confidence: 81%

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury

et al. 2022

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Traumatic peripheral nerve injuries tend to be more common in younger, working age populations and can lead to long-lasting disability. Peripheral nerves have an impressive capacity to regenerate; however, successful recovery after injury depends on a number of factors including the mechanism and severity of the trauma, the distance from injury to the reinnervation target, connective tissue sheath integrity, and delay between injury and treatment. Even though modern surgical procedures have greatly improved the success rate, many peripheral nerve injuries still culminate in persistent neuropathic pain and incomplete functional recovery. Recent studies in animals suggest that botulinum neurotoxin A (BoNT/A) can accelerate nerve regeneration and improve functional recovery after injury to peripheral nerves. Possible mechanisms of BoNT/A action include activation or proliferation of support cells (Schwann cells, mast cells, and macrophages), increased angiogenesis, and improvement of blood flow to regenerating nerves.

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Section: Attributes Of Bont/a That Make a Promising Therapeutic Agent...supporting

confidence: 81%

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury

et al. 2022

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“…Blocking neuromuscular transmission with BoNT/A, despite no injury to the motor axon, induces chemodenervation with a massive axon sprouting and neuromuscular junction remodeling [6,7]. Botulinum neurotoxin chemodenervation mimics axotomy, including the interruption of neurotransmission, induction of motor axon sprouting and upregulation of regeneration-associated proteins [8]. In rats, within a few days of the BoNT/A blocking, sprouts of the motor axons grow out over the surface of the muscle [7].…”

Section: Introductionmentioning

confidence: 99%

Jitter Evaluation in Distant and Adjacent Muscles after Botulinum Neurotoxin Type A Injection in 78 Cases

Kouyoumdjian

Graça

Oliveira

2020

Toxins

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To study the jitter parameters in the distant (DM) and the adjacent muscle (AM) after botulinum neurotoxin type A (BoNT/A) injection in 78 patients, jitter was measured by voluntary activation in DM (n = 43), and in AM (n = 35). Patients were receiving BoNT/A injections as a treatment for movement disorders. Mean age 65.1 years (DM) and 61.9 years (AM). The mean jitter was abnormal in 13.9% (maximum 41.4 µs) of DM, and 40% (maximum 43.7 µs) of AM. Impulse blocking was sparse. We found no correlation of the mean jitter to age, BoNT/A most recent injection (days/units), number of muscles injected, total BoNT/A units summated, number of total BoNT/A sessions, beta-blockers/calcium channel blockers use, and cases with local spread symptoms such as eyelid drop/difficulty swallowing. Maximum mean jitter (41.4/43.7 µs) for DM/AM occurred 61 and 131 days since the most recent BoNT/A, respectively. The far abnormal mean jitter (32.6/36.9 µs) occurred 229 and 313 days since the most recent BoNT/A. We suggested that jitter measurement can be done after BoNT/A in a given muscle other than the injected one, after 8 (DM) and 11 (AM) months, with reference >33 µs and >37 µs, respectively.

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“…As previously described, motor neurons were differentiated and cultured on plates coated with poly‐D‐Lysine (P6407‐5MG, Sigma‐Aldrich) and laminin (23017‐015, Thermo Fisher) at a seeding density of 3.0 × 10 4 cells per well. [ 27 ] MNs were fed with complete neurobasal media (95% Neurobasal Media, Life Tech 21103‐049; 1% non‐essential amino acids, Corning 25025111; 1% Glutamax, Life Tech 35050–061; 1% N2, Life Tech 17502‐048; 2% B27, Life Tech 17504‐044) supplemented with 0.1% ascorbic acid (Sigma‐Aldrich A4403), 0.01% BDNF (R&D 248‐BD), 0.01% CNTF (R&D 257NT/CF), 0.01% GDNF (R&D 212‐GD), and 0.1% ROCK Inhibitor (Tocris 1254) by volume.…”

Section: Methodsmentioning

confidence: 99%

Advanced Materials in Wireless, Implantable Electrical Stimulators that Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration

Guo

D’Andrea

Zhao

et al. 2021

Adv Funct Materials

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Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post-operative electrical stimulation (ES) increases axon regrowth, but practical challenges, from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement, have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for a type of thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post-operative period. Afterward, rapid, complete, and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re-anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.

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Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models

Abstract: BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.

Cited by 13 publications

References 49 publications

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury

Jitter Evaluation in Distant and Adjacent Muscles after Botulinum Neurotoxin Type A Injection in 78 Cases

Advanced Materials in Wireless, Implantable Electrical Stimulators that Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration

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