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S. P. Christiansen, B. C. Anderson, L. K. McLoon; Botulinum Toxin Pre-Treatment Augments the Weakening Effect of Injection With Ricin-mAb35 in Rabbit Extraocular Muscle. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2839.
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We have previously shown that the immunotoxin ricin-mAb35 significantly reduces extraocular muscle (eom) strength. Botulinum toxin injection up-regulates the number of acetylcholine receptors against which ricin-mAb35 is targeted and therefore may improve the treatment effect of the immunotoxin. In this study, we examined eom force generation and duration of effect of pre-treatment with botulinum toxin, followed by an injection of ricin-mAb35 one, two or four weeks later.
Both superior rectus muscles of normal adult rabbits were exposed, and 5 Units of botulinum toxin was injected into one. The contralateral control muscle was injected with an equal volume of saline. After one, two or four weeks, the botulinum toxin treated muscles were injected with ricin-mAb35. Additional rabbits received injections of either botulinum toxin only or ricin-mAb35 only without a second injection. After 12 weeks, the rabbits were euthanized, and both superior rectus muscles were removed and assayed physiologically using an in vitro apparatus. Muscles were stimulated at 1, 10, 20, 40, 100, 150 and 200 Hz to determine differences of both twitch and tetanic force generation. Treatment and control superior rectus muscles from a separate group of animals were examined histologically.
Twelve weeks after these injection series, the co-treated muscles showed a significant decrease in twitch and tetanic force generation compared to controls and to the muscles treated with ricin-mAb35 only or botulinum toxin only. The shorter the interval between botulinum toxin pre-treatment and ricin-mAb35 injection, the more profound the weakening effect, especially at higher stimulation frequencies. In the muscles treated only with botulinum toxin, both twitch and tetanic amplitudes had recovered to normal at 12 weeks.
These results suggest that the up-regulation of post-synaptic nicotinic acetylcholine receptors following botulinum toxin injection increases the treatment effect of ricin-mAb35 which is targeted against these receptors. Pre-treatment of eom with botulinum toxin followed by ricin-mAb35 may be useful in clinical situations when more significant weakening is desired.
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