Comparison of the therapeutic indexes of different molecular forms of botulinum toxin type A.
Botulinum toxin is produced by Clostridium botulinum in three different molecular-weight forms: LL toxin, 900 kDa; L toxin, 500 kDa; and M toxin, 300 kDa. We isolated the M toxin, then compared its muscle-weakening efficacy with those of L+LL toxin and BOTOX both in vitro and in vivo. The twitch tension of the mouse isolated phrenic nerve-hemidiaphragm was used for the in vitro study. For the in vivo study, grip strength was measured in the toxin-injected legs. Undesirable muscle weakening was evaluated by grip-strength measurement in the contralateral leg. Concentration-response curves for effects on the phrenic nerve-hemidiaphragm showed that M toxin was 10 times more potent than L+LL toxin. The therapeutic index in vivo was 3- to 5-times higher for M toxin than for L+LL toxin or BOTOX, indicating a greater separation for M toxin between doses with local efficacy and systemic toxicity. These findings indicate that the M toxin preparation may have a better pharmacological profile than the conventional preparation.
Yoneda
Shinji
S
Research and Development Center, Santen Pharmaceutical Co., Ltd., Nara, Japan. shinji.yoneda@santen.co.jp
Shimazawa
Masamitsu
M
Kato
Masanori
M
Nonoyama
Akira
A
Torii
Yasushi
Y
Nishino
Hajime
H
Sugimoto
Nakaba
N
Kozaki
Shunji
S
Hara
Hideaki
H
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*
D019274:Botulinum Toxins, Type A