In July 2010 UK drug regulators approved Botox as a treatment for chronic type of migraine(1). The next to go was FDA (U.S. Food and Drug Administration), which made the same move in October last year(2). The use of botulinum toxin in prevention of migraine attacks has been discussed for more than 10 years but due to extensive research only now has it become possible to make full use of a substance associated mostly with cosmetic surgery.
Botox is a trade name for botulinum toxin, manufactured by Allergan Inc. in the US. Originally produced by the bacterium Clostridium botulinum, only A type toxin is used for medical reasons. OnabotulinumtoxinA, being the correct name of the discussed substance, is potentially lethal. When eaten in improperly prepared and stored meat products, it causes botulism, which can lead to flaccid paralysis and death. As the toxin attacks neuromuscular junctions, the main research path goes to releasing muscle spasms in various syndromes.
Botulinum toxin was firstly considered for therapy purposes by an ophthalmologist in 1960s. He used it to treat strabismus as well as blepharospasm and achieved success. Nowadays the spectrum of how to employ Botox is extraordinarily wide(3). Not only does it help to smooth wrinkles, but it is also used in such conditions as achalasia, anal fissure and incontinence due to neurogenic bladder. Moreover, botulinum is popular in neurology to handle dystonias or spastic disorders connected with cerebral palsy, Parkinson’s disease and multiple sclerosis. One of the most interesting uses of toxin A is axillary hyperhidrosis, which involves severe primary sweating.
Migraine is more than hard to treat. It is a serious disease that can spontaneously evolve from episodic into the chronic type. Chronic migraine (CM) is defined as headache frequency of more than 14 days a month. Its one year prevalence concerns around 2-4% of the general population(4). Chronicization into CM is still a mystery. It is thought that factors such as genetic predisposition, obesity, drug overuse or inappropriate lifestyle may contribute to the development of CM. When pharmaceuticals can no longer be used, but quite just the opposite withdrawal is recommended, drug topiramate or botulinum toxin injections come in handy(5).
Two major studies: PREEMPT1(6) and PREEMPT2(7) have proved that OnabotulinumtoxinA has a considerable potential to reduce severity of CM. Patients who had received multiple injections around the head and neck once in every 14 days, at the end of the trial observed a reduction of migraine days per month. The cumulative hours of headache also decreased. What is more, the first clinical programme showed that botulinum was safe, well tolerated and that treatmentrelated adverse effects were very rare. The results for Botox are, according to the authors of PREEMPT, significantly superior to placebo. Though some scientists suggest that they are rather modest as for a revolutionary therapy(8). Also the mechanism of how the symptoms are relieved is not clear(8).
But if we take into consideration the great discomfort and disability CM causes, even a little decrease of pain seems to be crucial for patients. Therefore Botox along with topiramate remains one of the greatest hopes for treatment of chronic migraines. Looking at its therapeutic potential, who knows how many other diseases can be cured by Botox in future.
3.Development of future indications for BOTOX. Brin MF http://www.ncbi.nlm.nih.gov/pubmed/19470342
4.Chronic migraine: comorbidities, risk factors, and rehabilitation. Negro A, D’Alonzo L, Martelletti P http://www.ncbi.nlm.nih.gov/pubmed/20865469
5.A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine. Cady RK, Schreiber CP, Porter JA, Blumenfeld AM, Farmer KU http://www.ncbi.nlm.nih.gov/pubmed/21070228
6.OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT 1 Chronic Migraine Study Group. http://www.ncbi.nlm.nih.gov/pubmed/20647170
7.OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, Silberstein SD, Brin MF; PREEMPT 2 Chronic Migraine Study Group. http://www.ncbi.nlm.nih.gov/pubmed/20647171
8. Botulinum toxin for the treatment of headache: a promising path on a “dead end road”? Delstanche S, Schoenen J.http://www.ncbi.nlm.nih.gov/pubmed/21114129
9. Botulinum neurotoxin in the treatment of headache disorders. Mauskop A. http://www.ncbi.nlm.nih.gov/pubmed/20816423