Assay of diffusion of different botulinum neurotoxin type a formulations injected in the mouse leg

Abstract

Botulinum neurotoxin type-A (BoNT/A) is very effective in the therapy of a wide range of human syndromes characterized by hyperactivity of peripheral cholinergic nerve terminals. Little diffusion of this toxin from the site of injection is commonly observed, but even minor changes in this property would greatly affect the validity of the treatment. Different pharmacological formulations of BoNT/A are available, and they may have different diffusion characteristics due to protein complex size, product format, and pharmacological properties. Here we assessed the extent of diffusion of three commercial preparations of BoNT/A: Botox (Allergan), Dysport (Ipsen), and Xeomin (Merz Pharmaceuticals) using a novel and highly sensitive test based on neural cell adhesion molecule (N-CAM) expression in muscle. N-CAM is a membrane glycoprotein that accumulates on muscle fibers after denervation and is not expressed in untreated adult muscle. This allows fine monitoring of the functional diffusion of this toxin, and the sensitivity of this assay is emphasized by the use of the mouse model because of the small muscle dimensions. The results presented here indicate that there is no significant difference between Botox, Dysport, and Xeomin with respect to diffusion into adjacent muscles in the mouse leg.

Field effect of two commercial preparations of botulinum toxin type A: A prospective, double-blind, randomized clinical trial

“…[24][25][26] Carli et al 24 showed no significant difference among ABO, ONA, and incobotulinumtoxinA injections in the FME of BoNTA in adjacent muscles. The effects of BoNTA in adjacent muscles depend on clinical, temporal, and EMG factors 26 and on physical aspects such as injection technique and muscle targeting.…”

Botulinum toxin A, brain and pain

“…Peripheral spread away from the site of toxin injection is not dependent on auxiliary proteins (Brodsky et al, 2012;Carli et al, 2009). BoNT/A traffic from periphery to the CNS via axonal route is discussed in Section 6.…”

Absorption and Transport of Botulinum Neurotoxins

“…Moreover, investigations on local injections of botulinum complex for a therapeutic purpose have confirmed that BoNT/A dissociates virtually immediately from ANTPs under physiological conditions [45,135]. Moreover, although BoNT remains relatively localized at the site of injection by binding to the local nerve endings, side effects of BoNT therapy have been observed due to toxin diffusion [26]. Most often, the undesired effects are related to local toxin diffusion to the adjacent muscles, but in rare cases, adverse effects occur in distant muscles or result in central effects or generalized intoxication [1,63,66,67,87,146,185].…”