Botulinum neurotoxins treatment

Dickerson, T.J. and Janda, K.D. 2006. The use of small molecules to investigate molecular mechanisms and therapeutic targets for treatment of botulinum neurotoxin A intoxication. ACS Chem. Biol. 1 359-369. 

Dodick DW. Botulinum neurotoxin for file treatment of migraine and other primary headache disorders From bench to bedside. Headache 2003 43(suppl l) S25-33. 

Adler, Oyler, Keller, and Lebeda provide an overview of botulinum neurotoxin action leading into a description of the syndrome known as botulism and a discussion of possible treatment options. Subsequently, Adler et al. develop purported terrorist or military anticipated use of botulinum neurotoxin and the threat thereof. This threat of use has led to investments in research that have achieved several major milestones... 

Treatment of the neurotoxin with metal chelators such as ethylenediamine tetraacetic acid (EDTA) inactivate most (80%) of the enzymatic activity, and large part (80%) of the lost activity can be restored with the addition of Zn " ions activity (Foran et al., 1994). Similar loss of toxic activity of type A botulinum neurotoxin was recently observed in our studies with the neurotransmitter release studies in PC 12 cells (F. -N. Fu, R. Lomneth and B. R. Singh, unpublished data). However, the loss of activity was not restored with the replenishment with Zn " ions. The loss of activity at least in part seems to be caused by the change in the polypeptide folding (Fu and Singh, 1995). 

Botulinum, a neurotoxin with muscle relaxant properties, is used in me treatment of strabismus. 

Sakaguchi G (1982) Clostridium botulinum toxins. Pharmacol Ther 19 165-94 Sankhla C, Jankovic J, Duane D (1998) Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections. Mov Disord 13 150-54 Schantz EJ, Johnson EA (1997) Botulinum toxin the story of its development for the treatment of human disease. Perspect Biol Med 40 317-27 Schiavo G (2006) Structural biology dangerous liaisons on neurons. Nature 444 1019-20 Schiavo G, Matteoli M, Montecucco C (2000) Neurotoxins affecting neuroexocytosis. Physiol Rev 80 717-66... 

Botulinum toxin is both a medication and a neurotoxin, produced by the bacterium Clostridium botulinum. It is the most toxic protein known. It can be used to treat muscle spasms, and is sold commercially under various names (Botox, Dysport, Myobloc, etc.). Botox Cosmetic and Vistabel are available for cosmetic treatment. The toxin protein consists... 

The t-SNARE SNAP-25 is also expressed in the P-cell and has been localized mainly to the plasma membrane (Sadoul etal., 1995). SNAP-25 was cleaved by treatment of SLO-permeabilized cells with botulinum toxins (BoNT) A or E. The two neurotoxins inhibited Ca "-induced insulin exocytosis but failed to abolish the process completely (Sadoul ef al., 1995). This could be due to the failure of the toxins to cleave SNAP-25 already complexed to other fusion proteins (escaping detection by Western blotting) or to the requirement for SNAP-25 at a penultimate step in insulin exocytosis. 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

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