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Miracle Poison: Can a Lethal Neurotoxin be a Therapeutic?
Botulinum neurotoxin, produced by the anaerobic bacterium Clostridium botulinum is the most potent biological toxin identified thus far. A minute amount of botulinum toxin can lead to botulism, resulting in paralysis of muscles, even in death.

Seven different sero­types of botulinum neurotoxin, designated A to ­G, are produced by different strains of C. botulinum bacteria. Those serotypes are antigenically diverse but similar in structure, molecular weight and mode of action.

The neurotoxin blocks the release of acetylcholine, the principal neurotransmitter at the neuromuscular junctions where a muscle fibre meets a motor neuron. This interferes with the transmission of nerve impulses from the central nervous system to the muscle, hindering the muscle responding to motor neuron activity. This paralyses the muscle, making it weak and unusable.

Therapeutic Use of the Deadly Toxin

Despite its deadliness, physicians worldwide consider botulinum toxin as the most effective treatment for numerous movement disorders related with increased muscle contraction. Only the type-A botulinum toxin is currently available for clinical use. Three different preparations of botulinum toxin A exist in the market, namely, OnabotulinumtoxinA (marketed as Botox & Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc).

The drug is injected in minute doses into affected muscles or glands where it induces localized muscle paralysis by inhibiting transmission of neurons. This mechanism enables the toxin to relieve neuromuscular disorders that cause spontaneous contractions of muscles. Subsequent injections given at regular intervals will usually be required following the initial dose.

FDA Approval for the Use of Botulinum Toxin type A

Botulinum toxin type A was first approved by the FDA in 1989. In a news release issued in 2009, FDA announced that
Quote: Botox, Myobloc, and Dysport are approved by the FDA for the treatment of a condition marked by repetitive contraction of the neck muscles (cervical dystonia). Botox Cosmetic and Dysport are approved by the FDA for dermatologic use in the temporary improvement in the appearance of frown lines between the eyebrows called glabellar lines. In addition, Botox is approved for the treatment of severe underarm sweating (primary axillary hyperhidrosis), crossed eyes (strabismus), and abnormal tics and twitches of the eyelids (blepharospasm).
In 2010 FDA accepted Botox injection for preventing chronic migraine in adult patients and recently in 2013, FDA expanded the use of Botox to treat overactive bladder in adults.

FDA requires all of the botulinum toxin products to display a boxed warning and a medication guide. FDA also notes that these different products are not interchangeable due to difference in the units used to measure the products.

Other Possible Uses of Botulinum Toxin type A

Pioneered in 1981 by Dr. Alan Scott, an ophthalmologist, a significant amount of researches has been done over the years on the medicinal use of botulinum toxin. A recent study published in the medical journal Neurology in July 2012, reported that the botulinum toxin type A can help prevent shaking in the arms and hands of people with multiple sclerosis.

Moreover, various studies suggest the use of the toxin to treat disorders such as spasticity and other forms of muscle overactivity, hemifacial spasm (automatic facial contractions), some voice disorders (adductor laryngeal dystonia), focal limb dystonias (such as writer’s cramp)etc. There is also evidence of botulinum toxin effectively in reducing lower back pain.

However, FDA has not yet approved the use of botulinum toxin products as a treatment of muscle spasticity.

Possible Side Effects

Patients may experience short-term and mild side effects such as general weakness of the injected muscle following treatment, pain at the injection site, symptoms imitating influenza, headache and stomach disorders. FDA reports that during clinical trials regarding urinary incontinence, urinary tract infections, painful urination, and urinary retention have also been observed. When used as a cosmetic, symptoms have been reported such as drooping eyelid or the incapability of closing the eyes lids, double vision, uneven smile etc.

A paper published in the Journal of American Academy of Dermatology in 2005 informs that 28 deaths due to use of Botox as a therapeutic agent have been reported to FDA between 1989 and 2003 though no deaths were reported from the cosmetic use of Botox.

FDA now requires the labels of the commercial toxin preparations to indicate that there is a risk of the diffusion of toxin into adjacent tissues following injection, thereby causing botulism-like symptoms. Those symptoms could include swallowing and breathing difficulties that can be life-threatening. However, FDA also notes that adverse effects of spread of toxin have not been reported when Botox is used at recommended doses.
Contradictory Research

A research published in the Journal of Biomechanics in 2011 raises questions about the therapeutic use of botulinum toxin A. It reports that clostridium toxin type A (Botox) can produce weakness in target and non-target muscles. The study also reveals that repeated injection of the toxin induced degeneration of muscles. This is the first report to reveal such adverse effects caused by the toxin during clinical use.

Another study suggests that botulinum toxin may not be useful for treating migraine. However, more research is required in order to come to a conclusion.

In Conclusion..

Due to its effectiveness and relative safety botulinum toxin A still holds grounds as an invaluable treatment for neuromuscular disorders. Yet, more insight is required on prolonged clinical use of the toxin, especially with children and adolescents.

1. Coté, T. R., Mohan, A. K., Polder, J. A., Walton, M. K., & Braun, M. M. (2005). Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. Journal of the American Academy of Dermatology, 53(3), 407.

2. Fortuna, R., Aurélio Vaz, M., Rehan Youssef, A., Longino, D., & Herzog, W. (2011). Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox). Journal of biomechanics, 44(1), 39-44.

3. Münchau, A., & Bhatia, K. P. (2000). Regular review: Uses of botulinum toxin injection in medicine today. BMJ: British Medical Journal, 320(7228), 161.

4. Naumann, M., So, Y., Argoff, C. E., Childers, M. K., Dykstra, D. D., Gronseth, G. S., ... & Simpson, D. M. (2008). Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review) Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 70(19), 1707-1714.

5. Prescott, L.M., Harley,J.P., and Klein, D.A. (2008) Microbiology-5th ed: pp 930, McGraw-Hill Higher Education.




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We all are mostly familiar of the brand Botox and its use in both the medical and cosmetic industry. But little do we know about other brands that consist of the same neurotoxin.

We have the brand Azzalure, which is primarily used for the temporary improvement of the appearance of severe vertical frown lines arising between the eyebrows. It is manufactured by Galderma (UK) Limited. The procedure is given to adults below 65 years old who have an important psychological impact due to such frown lines.

Next, we know of Dysport by Ipsen Limited, where it focuses on muscle spasm. It has the same indications as Botox, except that it’s not for those with hyperhidrosis, headache prevention in people with chronic migraines, nor is it for urinary incontinence.

Another brand with the botulinum toxin is Vistabel, which is again used mainly for cosmetic purposes. Its manufacturer is Allergan.

Xeomin, on the other hand, was introduced by Merz Pharma UK Limited. Like Dysport, its effects are concentrated on muscle spasm correction.

The most important info that a patient given with the toxin should know is that the drug can spread beyond the injection part and to other areas of the body. Not only that, symptoms of life-threatening effects can appear several weeks after the treatment.

Such patients should look out for vision problems, drooping eyelids, hoarseness of voice, loss of bladder control, severe muscle weakness, or difficulty swallowing, talking, or breathing.

Also, the botulinum toxin effects are actually just temporary. The symptoms that you had prior to the treatment may return 3 months thereafter. However, when you get to have repeated injections, your body will in turn develop more antibodies against the toxin and may take lesser time for the prior symptoms to come back. That is why the use of the medication should be at least three months apart.
Lyka Candelario, RN
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Miracle Poison: Can a Lethal Neurotoxin be a Therapeutic?00