How does Botox work?

Botulinum Toxin (BoNT-A) is a neurotoxin secreted by  Clostridium Botuli and purified to be used in therapeutics. There is seven serotypes of BTX ( A,B,C,D,E,F,G) but only  BoNT-A and BoNT-B are licensed for focal dystonia treatment.

BoNT-A is a polypeptide with  2 chains linked by a disulfure bridge. The heavy chain is responsible of the specific binding of the BoNT-A to the cholinergic fibers. The limited action on cholinergic fibers due to this specific bindings is one factor of safety of the BoNT-A . The light chain is responsible of the enzymatic action of the BoNT-A, which cuts a membrane vesicule protein ( called SNAP-25), making the release of the acetylcholine in the synaptic cleft impossible.

When the release of the acetylcholine is blocked, there is no more signal from the nerve to the muscle , therefore the muscle is less able to contract. Also there is no more signal btween the nerve and the glands ( sweat or salivary glands for example), and the gland stops secreting. This blocage of the release of the acetycholine is transient, as there is  sprouting of the nerve terminals and also synthesis of new membran vesicule proteins.

Enhancing the effect of BoNT-A?

The enzyme activity of the BoNT-A  requires the presence of Zinc and they have been some suggestion that taking Zinc before the injection could influence the effect of the BoNT-A but there is no study to support  this practice.

There is physiological study on frog diaphragm model (Hughes and Whaler, 1962) which showes that  stimulation of the nerve, responsible of the muscle contraction, increased the effects of the BoNT-A on the muscle as more BoNT-A is capted when the nerve is excited. It may explain why the first inejction is always described as the most powerful by the patient as initially the dystonic muscle is very active. Also, it may justify, that the patient following imediately the injection, is asked for the next 30 minutes to activate his dystonic muscles such as writing or playing an instrument.

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