Assay of diffusion of different botulinum neurotoxin type a formulations injected in the mouse leg.
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.
Carli
Luca
L
Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, Padova, Italy.
Montecucco
Cesare
C
Rossetto
Ornella
O
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000378:metabolism* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000145:classification; D005786:Gene Expression Regulation / Q000187:drug effects; D006614:Hindlimb; D007273:Injections, Intramuscular / Q000379:methods; D008297:Male; D051379:Mice; D018908:Muscle Weakness / Q000139:chemically induced; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009460:Neurologic Examination / Q000379:methods; D009465:Neuromuscular Agents / Q000378:metabolism* / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution
D019006:Neural Cell Adhesion Molecules; D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A