Knock-out blows for Botox
Sylvester Stallone’s last film in the Rocky series featured him finely Botoxed and de- wrinkled, with plumped lips and beefed-up muscles that had film critics speculating about steroid overdosing. Not just Americans have gone Botox-mad. The whole age-conscious world is queuing for injections of this non-surgical cosmetic therapy for crow’s feet around the eyes and deep trenches on the brow. Botox is one of the trade names for botulinum toxin which, used in tiny amounts and injected directly into the tissue, temporarily paralyses the muscles and so relaxes the skin, thereby reducing wrinkles.
But there is more to Botox than meets the eye. According to its makers, the transnational US-based company Allergan whose total product sales topped 4.3 billion last year , the drug is clocking up an impressive list of new medical uses to treat some 21 different conditions in patients. More uses are being found all the time. The list includes post-stroke muscle spasms (spasticity) and severe neck and shoulder contractions, known as cervical dystonia.
It was reported from Australia recently that after 23 years in a wheelchair, stroke victim Russell McPhee, 49, is walking again thanks to Botox. Regular shots in the arm and legs had the effect of relaxing muscles which had been in permanent spasm. Despite the pain of starting over, McPhee regained muscle strength and mobility and after 18 months he can walk around his home unaided.
Doctors said they had seen similar results in more recent stroke victims but what was remarkable in McPhee’s case was that he was able to regain movement decades after being immobilised.
Botox and its competitors including Vistabel, Dysport, Myobloc, Neurobloc and Xeomin are being tried out by doctors in a great variety of ways that reach far beyond the aesthetics of how you look and feel. What business theorists call “user innovation” — the tendency of people to find new uses for products that were not foreseen or intended by the makers — it turning the toxin into a marvel of medicine.
Botox was first approved by the US Food and Drug Administration (FDA) in 1989 to treat two eye muscle disorders — uncontrollable blinking (blepharospasm) and misaligned eyes (strabismus). Botulinum toxin is in fact a neuromodulator which alters the way nerves transmit impulses to the muscles, and despite being one of the most potent poisons known to us, it has the potential to treat several serious illnesses.
But before anyone gets too excited about this new wonder-drug-to-be, there are side-effects which cannot be easily dismissed — especially by the hordes of anti-ageists who flock to wrinkle clinics daily. Apart from nausea and possible swelling (one woman said the treatment left her looking like a Neanderthal) the most worrying research findings suggest that botulinum toxin could remain in the nervous system for a long time. Are there potentially devastating long-term effects? Nobody knows, but one thing is for sure: Botulinum neurotoxin (BoNT), is what scientists and chemical warfare experts describe as a Category A biothreat agent. According to Dr Prabhati Ray of the Walter Reed Army Institute of Research in the US, it is the most potent poison known to mankind. Currently no antidote is available to rescue poisoned nerve synapses or connections.
Botulism, a form of food poisoning, has been known for centuries as potentially fatal. In the 1870s, a German physician by the name of Muller derived the name botulism from the Latin word for sausage as it was first associated with German sausage. Microscopes revealed the bacteria known as Clostridium botulinum in 1895, and in the 1930s the neurotoxin that it produces was identified, in time for troops serving in World War 2 to be protected form eating contaminated canned food.
As little as one nanogram (one billionth of a gram) per kilogram of botulinum toxin can kill a person, and scientists have estimated that about one gram could kill a million people. This is not a poison to be played with. And yet, as a chemical messenger that modifies nerve function, it has proven therapeutic properties if used in tiny amounts. The problem is that the toxin has been shown to persist in the bodies and brains of rats, which raises serious questions about its use by humans.
A study in the Journal of Neuroscience in April 2008 confirmed that the widely used botulinum neurotoxin type A (sold under commercial brand names such as Botox) can move from the original injection site into the central nervous system. Dr Matteo Caleo, of the Institute of Neuroscience under Italy’s National Research Council, confirmed the movement of botulinum neurotoxin A by detecting the remnants of proteins it had fragmented.
These findings contradict previous research, which suggested that botulinum neurotoxin was completely degraded at the injection site and not transported beyond it. Botulinum toxin was injected into the whisker muscles of rats. Within three days, active forms of the toxin had migrated to the brain stem, into the brain, and back to the eye.
Caleo and colleagues noted in particular that the effects of the botulinum neurotoxin injection on the hippocampus (part of the forebrain) were still present six months later. This was alarming news — at least for those in the scientific community who had wondered what kind of dangerous game humanity was playing with its cosmetic panacea.
In any case, Matteo and colleagues are not out to wreck the industry but, like others, to explore the positive powers of botulinum toxin for clinical uses.
Armed with the knowledge that the botulinum toxin does not fully disappear, scientists can now begin to seek ways of preventing it from spreading.
Reacting to the Italian study, Dr David Sherry of the University of Oklahoma Health Sciences Centre, suggested that side effects could be prevented by blocking the toxin’s transport into the tips of nerve cells or back across the nerve cells.
The course of innovation never runs smooth. Botox and its competitors have so far proved to be a boon for humanity and both the companies that produce the drug and the doctors and patients who use it — for aesthetic or therapeutic reasons — are unlikely to let go. The search is on for a Botox blocker.
Published: 2009/07/22
Business Day – BioChemistry Section
