Botulinum toxin, better known as botox, is one of the most toxic biological substances known to man. Despite this, this neurotoxin plays a significant role in the treatment of many medical conditions, and the use of botox is considered one of the safest aesthetic procedures. What exactly is botulinum toxin and why is it considered a miracle poison?
Bacterial neurotoxin
Botulinum neurotoxin, or BoNT, is a product of the anaerobic, gram-positive bacterium Clostridium botulinum. C. botulinum produces seven antigenically and serologically different toxins (A – G), of which types A and B are in medical use today. The spores of this bacteria are very resistant and survive in conditions without oxygen, which means that they can contaminate improperly preserved food and create their own toxins there. In the case of consuming such food, a rare but life-threatening disease – botulism – can occur. Botulism causes serious neurological symptoms, including muscle weakness and paralysis, difficulty speaking, swallowing and breathing, double vision, dry mouth and other similar problems. It is treated with the use of a specific antidote; the recovery is long and rehabilitation is often required to restore muscle strength and function.
Structure and mechanism of action
Botulinum toxin is a protein complex consisting of a biologically active part and inactive complexing proteins. The biologically active part is composed of a light L chain and a heavy H chain. Through the H chain, the toxin selectively and irreversibly binds to receptors on presynaptic cholinergic neurons. The toxin-receptor complex then enters the neuron by the process of endocytosis. When the pH in the endosome is lowered, the disulfide bond between the L and H chain breaks and the neurotoxin is released into the cytoplasm. The L chain then interacts with cellular proteins such as SNAP-25 (synaptosome-associated protein), which are responsible for the exocytosis of vesicles containing the neurotransmitter acetylcholine. The result is inhibition of acetylcholine secretion and consequent muscle paralysis.
Medical application
Botulinum toxin is best known for its use in aesthetic medicine as a rejuvenating treatment, but its application is in reality much broader. BoNT-A was first used by ophthalmologists to treat strabismus, a disorder of the position of the eyes. After that, it began to be widely used in neurology in patients with excessive muscle contractions and movement disorders such as dystonia. Today it is indicated for the following disorders:
Neurological disorders
BoNT-A is used to alleviate the symptoms of spasticity in children with cerebral palsy and in adults after a stroke. Its usage is also found in the treatment of other spasticity such as blepharospasm (eye muscle spasm) and hemifacial spasm, as well as in relief of chronic migraine symptoms.
Bladder disorders
BoNT-A is indicated for idiopathic overactivity of the urinary bladder and for urinary incontinence in adults with neurogenic overactivity of the detrusor muscle resulting from a neurogenic bladder due to stable subcervical spinal cord injury or multiple sclerosis.
Disorders of the skin and adnexa
In particular, BoNT-A is indicated for persistent and severe primary hyperhidrosis (excessive sweating), which interferes with daily activities and is resistant to topical treatment.
Side effects and safety
Side effects from BoNT-A administration occur in the first few days after administration, are rare and transient, but can last for several months or longer. Expected side effects include local muscle weakness, in accordance with the mechanism of action of botulinum toxin, as well as pain, inflammation and swelling at the injection site. Systemic side effects, such as generalized weakness and flu-like symptoms, rarely occur.
Although botulinum toxin is a poisonous substance, proper doses applied to the correct sites are safe and effective. Improper use can cause muscle weakness and difficulty swallowing or breathing, which can have fatal consequences. Therefore, it is very important that the injections are administered by qualified and experienced professionals.
A miraculous poison
Botulinum toxin is a great example of a toxic substance with serious consequences that has been repurposed for medical purposes and is now helping people around the world. In the future, there will be no limits to the possibilities of clinical application of this neurotoxin. Newer research points to its potential use in the treatment of pain and mental illnesses such as depression. Scientific research is continuously discovering more and more about this miraculous poison and opening up new possibilities for its therapeutic application.
References
2. França K et al. The history of Botulinum toxin: from poison to beauty. Wien Med Wochenschr. 2017, 167(Suppl 1), 46-48.
3. Botulinum Toxin: Essential Facts for Patients, 2018., https://www.movementdisorders.org/, accessed on 19. 1. 2024.
4. Botulinum Toxin, 2022., https://www.medscape.com/, accessed on 19. 1. 2024.
5. Sažetak opisa svojstava lijeka – Botox [Summary of product characteristics – Botox], 2023., https://www.halmed.hr/, accessed on 19. 1. 2024.