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BRAIN and NERVE Volume 63, Issue 7 （July 2011）

BRAIN and NERVE 63巻7号（2011年7月発行）

Japanese English

増大特集神経筋接合部―基礎から臨床まで

ボツリヌス毒素の治療への応用 Clinical Application of Botulinum Toxin 目崎高広 ¹ Takahiro Mezaki ¹ ¹榊原白鳳病院神経内科 ¹Department of Neurology,Sakakibara Hakuho Hospital キーワード： botulinum toxin , therapy , remission , ultrasonography , molecular engineering Keyword: botulinum toxin , therapy , remission , ultrasonography , molecular engineering pp.785-794

発行日 2011年7月1日 Published Date 2011/7/1

DOI https://doi.org/10.11477/mf.1416100960

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はじめに

　ボツリヌス毒素の治療への応用は，まだボツリヌス症（botulism）の本態が未解明であった1822年に，ドイツ人の医師であり詩人であったKernerによって示唆されていた。Kernerは食餌性ボツリヌス症の症候を詳細に記載した人物である。その観察から，この食中毒の原因物質が生体にどのような作用を及ぼし，どのような不具合を改善させ得るのかを推定したのであった^1）。Kernerが挙げた対象疾患には，小舞踏病（Kernerの記載ではいわゆる聖Vitus舞踏病），体液・汗・粘液の過剰分泌，悪性疾患による潰瘍，火傷後の皮膚損傷，妄想，狂犬病，ペスト，肺結核による消耗，黄熱病などがある。このうちのいくつかは現在のボツリヌス毒素療法（ボツリヌス療法）の対象になっている。

　本稿では，神経筋接合部遮断による骨格筋麻痺作用の治療応用のほか，ほかの機序を利用した治療の試みについても解説する。

Abstract

　The clinical application of botulinum toxin (BoNT) was first proposed by Justinus Kerner in 1822.　BoNT was formally accepted as a therapeutic agent in the 1970s, and currently, it is used worldwide for treating diseases as well as for cosmetic conditions.　In Japan, Botox^® is the only type A formulation that has been officially approved for the treatment of blepharospasm, hemifacial spasm, cervical dystonia, pes equinus of cerebral palsy, adult spasticity of upper and lower limbs, and Botox Vista^® is applied for glabellar frown lines.　Its effect is symptomatic, but long-lasting remission is noted after treatment in more than 30% of cases with cervical dystonia.　Ultrasound guidance is useful and may be even superior to electromyographic monitoring, especially when the obliquus capitis inferior muscle is targeted in rotatocollis, because the vertebral artery or upper cervical nerve root(s) may be injured when the needle penetrates the muscle.　BoNT alleviates pain or glandular secretion besides causing a neuromuscular block.　After being transported to the axons, BoNT is carried centrally and even to the adjacent neurons via synapses (toxin jump).　A direct central action has also been postulated.

　BoNT is generally safe, but serious adverse reactions may occur very rarely.　Individual differences in toxin sensitivity may be considerably greater than assumed, and even the routine clinical dose may be too high in some patients.

　The future strategy includes clinical application of other types of toxin or chimera toxins,or the use of the toxin as a cargo ("Trojan Horse") carrying some bioactive molecules into the cell.　A non-injection procedure for mucosal application or cosmetic use is currently under clinical trials.