Botulinum neurotoxin: poison turned palliative

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¢ ay October 1996 (10)- VoL 2, No. 10, pp. 405-446 Botulinurn neurotoxins: mechanism of action and

neuro oxi'n{ poison

by Cesare Montecucco, Giampietro Schiavo,

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turned palliative

One of {he first cases of infant botulism diagnosed by Dr S|ephenS. Amon al fl~eCMifimfia Depamnemof Heahh Sere°vices.Berkele). CA. LISA: l'epmduced wit} pemussion

of Dr Am~.~.

The most lethal poison known to man is used c u ~ m l y in the

418

Adhesion of muitipM mye0oma cells to the bone marrow microenvironment: implications for future therapeutic strategies, by Maria B. Vidriales and Kenneth C. Anderson Bone marrow ofa paliem wifll muMpie myeloma,

~2~

Neurotrophin receptors, tumor progression and t u m o r maturation,

by Sven P~hlman and Jeff C. Hoehner

432

Recombinant immunotoxins: protein engineering for cancer therapy,

by Ulrich Brinkmann ~' Ribbon diaglam o! ihc |¢coflibittatl|HIlO|l|ill¢}|oXill

B3(Fv)-.,,,PE38(iMB-7).

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Coming next month in Mi iT @ Growth factors and cytokines in hair follicle development

and cycling: recent insights from animal models and the potentials for clinical therapy @ Juvenile myelomonocytic leukemia: molecular understanding and prospects for therapy @ Developing particle-mediated gene-transfer technology for research into gone therapy of cancer 0 Interleukin 8 as a novel target for irtervention therapy in acute inflammatory disease Breast cancer prevention strategi£s for the twenty-first century

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clinic to ~rea~a variety of mu~le spasm disorders, mid the number of experimental therapies continues to rise. Only recently has basic research brought to light the molecular mechanism whereby botuiinunl neurotoxin blocks nerve function. The review by Ces~e Monteeucco and colleagues in this issue of MMT describes butulism as a disease, explains cmTem infommtion on toxin structure and intracellular action, and discusses clinical applications of the toxin. Focal clinical admhfistradon of this toxin leads to mescle weakening ~ d amelioration of a number of muscle spasm disorders, although variations in omcome remain° Further developmem of standardized and clinically memfingful assays of toxin potency, as well as technical advances in toxin administration, should improve theral~utic reliability. Contempora.q~ research is aimed at a more complete understanding of the molecular evems required to deliver the toxin to i~ intracellular sile of aclion, to produce the maximal effect of the toxin in blocking neurotransmitter release, and m recover nerve function f~41owing intoxica|mn. Eme~ging information promises advances no~ only in the treatnmnt of botulism, bm also in the efficacy of i|s use as a dmrai~ntic agent. Protein engineering conM lmtentially ct'cate a modified |oxin of g~ea~r po~ncy a~d leng~kcned intraceilular half life. The effect of botulinum neurotoxins on membrane fusion events has also attracted the attention of cell and neurobiologists interested in protein delivery and membrane tratlieking. Understanding botulism with today's technology will provide a valuable tool for both modem cell biology and medical practice. Elaine A. Neale ~ D Chief, Section on Cell Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA.

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