Botulinum Toxin (BOTOX) Could Affect More Than the Target Nerves

Highlights

• Botulinum toxins which include the popular BOTOX are extremely potent
• The mode of action of these toxins is to cancel the transfer of signals to nerves which leads to paralysis that lasts for a few months.
• The toxin is now found to move beyond the site of injection, raising concern about effects on other parts of the body.
Botulinum toxins are highly potent neurotoxins that are produced by the organism Clostridium botulinum.




Mechanism of Action

The toxins interfere with the transmission of neural signals by preventing the release of acetylcholine. Acetylcholine has a pivotal role in the neuromuscular junction where it is the principal neurotransmitter. The toxin takes about 24 to 72 hours to produce an effect.

‘The use of Botulinum toxin should be carried out with caution.’

Medical Uses of Botulinum Toxin - BOTOX

The following medical conditions are treated using the toxin

• Hemifacial spasms (rare neuromuscular disease)
• Strabismus (misalignment of the eyes)
• Spastic movement disorders
• Hyperhidrosis (increased sweating)
• Focal dystonias
• Hypersalivation (excessive saliva production)

The toxin is also used for cosmetic purposes like correction of wrinkles, lines and creases found on the face, neck, chin and chest.

Botulinum toxin is used for medical and cosmetic purposes as it was believed to be completely safe, with its effect restricted to local nerves. Edwin Chapman, researcher from The Howard Hughes Medical Institute who also works as a professor at the University of Wisconsin-Madison in the neurosciences department, says "The idea was that they are safe to use, they stay where they are injected, and you don't have to worry about toxin going to the central nervous system and causing weird effects."

Movement of the Toxin Beyond the Injection Site

The first seed of suspicion that the toxin was moving beyond the site of injection began in 2009. The Food and Drug Administration (FDA) included the following warning

• "To highlight that botulinum toxin may spread from the area of injection to produce symptoms consistent with botulism"
• "Unexpected loss of strength or muscle weakness. � Understand that swallowing and breathing difficulties can be life-threatening and there have been reports of deaths related to the effects of spread of botulinum toxin."

Disparities Observed while Treating Medical Conditions

Cervical dystonia leads to spams in the neck muscles. The injection of the Botulinum toxin provides relief to the patient, though local effects for the relief cannot be explained.

Current Laboratory Study Highlights Remote Effect of Botulinum Toxin

The study by researchers Bomba-Warczak and colleagues and published in The Journal The Cell Reports focuses on the remote effect of the Botulinum toxin. The study used mouse neurons growing in wells and which were connected by tiny channels that allowed the axons to grow.

The toxin was injected into certain wells that contain the mouse neurons. They helped in cleaving protein that was responsible for the fusion of vesicles. This fusion leads to paralysis. The researchers used anti-bodies against the cleaved proteins to detect the effectiveness of the toxin.

The effects of the toxin were found in wells into which the toxin wasn't injected, signifying the remote effects of the toxin. Dr. Chapman says "Every time one fraction of the toxin acts locally (on the first nerve cell it contacts), another fraction acts at a distance. It's unknown how far they travel, which likely depends on the dose of toxin and other factors."

Dr. Chapman also adds "We have seen that these toxins enter neurons at the injection site, causing the desired local paralysis, but Ewa and Jason have shown unambiguously the existence of a second entry pathway that takes some of the toxin molecules to other neurons."

Possibility of a Genetically Engineered Toxin

The researchers claim that genetically engineered toxins could be created that attach to the receptors of the local nerves into which they are injected and which are unable to travel to other neurons.

Dr. Chapman believes that doctors would refrain from prescribing the Botulinum toxin to patients if there is a possibility that it could affect other areas. While he says "It's an exciting prospect, supplanting a $2 billion drug with a safer drug," it remains to be seen if the genetically modified drug proves to be effective and viable.

Reference:

1. BOTULINUM TOXIN - (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856357/)
Source: Medindia

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