Monday, 29 July 2013

Botulinum: from Toxin to Treatment tool

Botulinum is a highly poisonous exotoxin secreted mainly by the bacterium Clostridium botulinum. There exist 7 serotypes of botulinum toxins, from toxin A to toxin G each differing in their potency and receptors to which they bind. Structurally, these comprise of 2 different protein chains- the A chain and the B chain which are joined together by a disulfide bond. These toxins act at the neuro-muscular junctions and are hence called neurotoxins. They prevent the release and uptake of the neurotransmitter acetylcholine, which is responsible for muscle contraction. As a result of this, the person suffers from flaccid paralysis. Functionally, the neurotoxin can be said to comprise of three domains - a receptor binding domain, a translocation domain and a catalytic domain. The B chain (or the binding domain) attaches to the receptors on the neurons facilitating the entry of the A or active domain into the cell by cleavage of the disulfide bond.. Although it still not clear how this is achieved, it has been presumed that the translocation domain forms a channel to facilitate the entry of the A chain into the cell.

When administered in very small quantities,the toxin effect is reversible and largely restricted to the affected area. It may take anywhere between 8 weeks to 6 months for the effect of the toxin to subside. Due to these factors it has increasingly found use as a treatment tool in various disorders and afflictions. The most famous of all would definitely be BOTOX!

It was in 1989, that BOTOX was approved by FDA to treat disorders like strabismus (squint eye), blepharospasm (abnormal twitching of eyelid), and hemifacial spasm (involuntary muscle contractions on one side of face). The botulinum injection is given at the site of affected muscle. In delicate places, the process is aided by electromyography. The machine detects the point of increased electrical activity thus indicating the site where the injection must be given. Another disorder where BOTOX is used is cervical dystonia (involuntary movement of the neck). Along with BOTOX, Dysport is another marketed botulinum toxin that can be used to treat cervical dystonia. Both these preparations are made from botulinum toxin A. However, some people may develop antibodies against toxin A and then they may be given the botulinum toxin B preparation marketed as MyoBloc (in US) and NeuroBloc (in Europe).

It was only in the year 2002 that BOTOX was approved by FDA for cosmetic treatments with which it is today synonymous. In addition, botulinum toxin A is also used as a treatment tool for axillary hyperhidrosis (excessive sweating) and detrusor overactivity. The botulinum toxins are also under experimentation for hypersalivation, wound healing, chronic musculoskeletal pain , just to name a few. Efforts are also underway to engineer novel recombinant botulinum toxins with improved efficiency.


References:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856357/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496996/#!po=6.25000

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