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S.P. Christiansen, B. Anderson, L.K. McLoon; Combining Ricin–mAb35 and Botulinum Toxin to Weaken Extraocular Muscle . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5395.
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The pharmacological treatment of strabismus may be improved if the duration of treatment effect can be increased. We have shown previously that a single injection of the immunotoxin ricin–mAb35 substantially weakens extraocular muscle for at least 12 weeks. We tested whether combined treatment with botulinum toxin and ricin–mAb35 would augment the muscle weakening effect of either agent given alone.
One superior rectus muscle of each adult rabbit was injected with either 5 units of botulinum toxin, 1/50th MTD ricin–mAb35, or 5 units of botulinum toxin followed 3 days later by an injection of ricin–mAb35. The fellow superior rectus muscle was treated with normal saline. After 4 weeks, the animals were euthanized, and both superior rectus muscles were removed and assayed physiologically using an in vitro apparatus.
At four weeks after a single injection of botulinum toxin, twitch force generation was reduced 20 to 30% of control muscles. Treatment with ricin–mAb35 alone reduced twitch force by 80% compared to control and 70% compared to botulinum toxin only. At tetanic stimulation, muscle force was reduced by 20 and 40% respectively. The combined treatment of botulinum toxin and ricin–mAb35 resulted in lower muscle force generation at all stimulation frequencies compared to botulinum toxin only, and lower muscle force generation at the lower stimulation frequencies when compared to ricin only.
Botulinum toxin is known to result in neurite sprouting within the paralyzed muscle. The rationale behind this experiment is that injection of ricin–mAb35 at a time when there is an upregulation of neuromuscular junction number should increase the efficacy of muscle weakening by these agents. We are currently testing different intervals between injection of botulinum toxin and injection of ricin–mAb35 to determine if this combination can be made even more effective. Optimizing methods that extend treatment duration may make combination drug treatment clinically useful.
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