A brief history of neurological botulinum toxin therapy in Germany.

Botulinum toxin (BT) has long been infamous in food safety and biological warfare. In the early 1970s, Alan B Scott of San Francisco invented its therapeutic use originally in extraocular eye muscles to treat strabismus using a therapeutic BT type A preparation provided by Edward J Schantz and Eric A Johnson. Subsequently a large number of medical indications based on motor and glandular hyperactivity and-most recently-chronic migraine are now treated by BT therapy. BT's highly specific and elaborate mechanism of action represents a completely novel therapeutic principle which will have consequences far beyond existing indications. BT therapy entered neurology through Stanley Fahn in New York from where C David Marsden brought it to London. From here neurological BT therapy came to Germany through Reiner Benecke and Dirk Dressler. Ophthalmological BT therapy was brought directly to Germany by Peter Roggenkämper, a fellow of Scott. By the early 1990s, several users in Germany had learned about BT therapy and made the country one of the most productive countries in clinical BT science-backed up by a long tradition of solid basic BT research. For several years now, however, BT therapy in Germany has been stagnating due to a lack of reimbursement for the medical treatment and due to off-label use challenges.

The history of Botulinum toxin: from poison to beauty.

Botulinum toxin, also called the "miracle toxin," is a neurotoxin produced by the bacteria Clostridium botulinum. It is known to block nerve signals that contract muscles resulting in a temporary paralysis of the muscles. Toxins type A and B have been extensively studied and utilized in the realm of beauty and cosmetology. Initially, the toxin gained popularity as a disease-causing "poison". It was only later that it found its way to becoming a must have in modern aesthetic practice. Today, this wonder toxin has proven to be an apt and convenient option in the field of anti-aging medicine.

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature.

Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

Botulinum toxin drugs: brief history and outlook.

The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur.

[The route of botulinum toxin from cause of food poisoning to medical remedy]. / Botuliinin tie ruokamyrkytyksen aiheuttajasta lääkkeeksi.

Botulinum toxins are amongst the most poisonous substances known in nature. The discovery and development of this toxin into a medical remedy is one of the most fascinating stories in the history of medicine. German physician Justinus Kerner founded the theory of treating hyperactive disorders with botulinum toxin and Alan Scott was the one to make this happen successfully. Nowadays the toxin is widely used in different indications, and the research is still going on for discovering novel tools for treating e.g. pain.

Learning from the past: historical aspects of bacterial toxins as pharmaceuticals.

Botulinum neurotoxins are the most poisonous substances known to humankind, but also are the bacterial toxins most frequently used as pharmaceuticals to benefit humans. The discovery of botulinum toxins and development into a useful drug is unique and fascinating, dating back to the early 19th century, when Justinus Kerner first recognized that botulism was caused by a biological toxin and suggested its use for medicinal purposes. This was translated into reality in 1980, when Alan Scott for the first time used the toxins to successfully treat strabismus. Now a subset of botulinum toxins are widely used for cosmetic applications, treatment of various movement disorders, pain and many other syndromes, and further developments using other botulinum toxins or recombinant molecules engineered from subdomains are promising.

Botulinum toxin historical aspects: from food poisoning to pharmaceutical.

BACKGROUND: In the history of medicine, unexpected coincidences indicated the development of new treatment options. OBJECTIVE: One of the most peculiar ones concerns the finding of botulinum toxin, and this should be familiar to physicians using the drug. METHODS: A survey through the history of the "fat-poison" has been performed. RESULT: A poison turned to one of the most popular drugs in aesthetic medicine. CONCLUSION: Depending on the dose, a substance may be poisonous or not.

The unusual history and the urological applications of botulinum neurotoxin.

INTRODUCTION: Botulinum neurotoxin (BoNT) is probably the most potent biological toxin that can affect humans. Since its discovery by Justinus Kerner, BoNT has seen use in a wide range of cosmetic and non-cosmetic conditions such as cervical dystonia, cerebral palsy, migraines and hyperhidrosis. We tried to trace its history from its inception to its recent urological applications. MATERIALS AND METHODS: Historical articles about botulinum toxin were reviewed and a Medline search was performed for its urological utility. We hereby present a brief review of historical aspects of BoNT and its applications in urology. RESULTS: In 1793, the first known outbreak of botulism occurred due to 'spoiled' sausage in Wildebad, Germany. The German physician and poet Justinus Kerner published the first accurate description of the clinical symptoms of botulism (sausage poison). He was also the first to mention its potential therapeutic applications. In urology, BoNT has been used in bladder and urethral lesions with varying degree of success. Recently, BoNT applications were explained for prostatic disorders. BoNT applications in urology are in the treatment of detrusor external sphincter dyssynergia, detrusor overactivity, detrusor underactivity, spastic conditions of the urethral sphincter, chronic prostate pain, interstitial cystitis, non-fibrotic bladder outflow obstruction (including benign prostatic hyperplasia) and acute urinary retention in women. CONCLUSION: Justinus Kerner is the godfather of botulism research. The role of BoNT in urology has evolved exponentially and it is widely used as an adjuvant in voiding dysfunction. In the future, its utility will broaden and guide the urologist in managing various urological disorders.

[Botulinum toxin: from drug to poison]. / Botulinum Toxin: vom Medikament zum Toxin ...

For most of its time, the history of botulinum toxin (BT) has been the history of botulism, i. e. of an intoxication with BT. By the end of the 1960's a paradigm shift took place which in this radicalness had never occurred before in the history of mankind. At that time BT was first used therapeutically to treat strabismus. From ophthalmology BT rapidly spread into numerous medical specialties. For most of its indications BT is the therapy of choice, for some it has revolutionized their treatment altogether. The widespread therapeutic use of BT allowed detailed clinical and technical investigations of BT's action upon the human body. Applying this knowledge we diagnosed for the first time chronic botulism in adults living on a farm with chronic bovine botulism. This constitutes another radical paradigm shift. The history of BT is the history of a dual paradigm shift each time induced by a complete reversal of the viewing perspective. Knowledge gain can be a linear process. It can, however, also be a circular one. Changes of the viewing perspective are crucial. Changing the viewing perspective may facilitate knowledge gain. This might be used to develop an instrument to facilitate knowledge gain.

From poison to remedy: the chequered history of botulinum toxin.

Botulinum toxin poisoning has afflicted mankind through the mists of time. However, the first incident of food-borne botulism was documented as late as the 18th century, when the consumption of meat and blood sausages gave rise to many deaths throughout the kingdom of Württemberg in South Western Germany. The district medical officer Justinus Kerner (1786--1862), who was also a well-known German poet, published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822 and attributed the intoxication to a biological poison. Kerner also postulated that the toxin might be used for treatment purposes. In 1895, an outbreak of botulism in the small Belgian village of Ellezelles led to the discovery of the pathogen "Clostridium botulinum" by Emile Pierre van Ermengem. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz in the early 1970s, when the type-A serotype was used in medicine to correct strabismus. Other preparations of the type-A toxin were developed and manufactured in the United Kingdom, Germany, and China, whereas a therapeutic type-B toxin was prepared in the United States. To date, the toxin has been used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain.

[Botulinum toxin, description and clinical applications in the treatment of the face wrinkles]. / La toxine botulique description et applications cliniques dans le traitement des rides du visage.

UNLABELLED: The botulinum toxin is used more and more in the treatment of the wrinkles of the face and mainly in its 1/3 superior part. OBJECTIVES: To describe the technique of injection and to establish a treatment program based on the anatomical data. MATERIALS AND METHODS: The description of the muscles and the elements constituting the face makes it possible to specify the play of the muscular balances of the face. RESULTS: The technique of injection needs certain requirements: It must be of small quantity and not diffuse. The treatment program must be integrated in a unit based on the study of each muscular group of the face and the opposite skin to release a reasonable attitude in the handling in safety of this toxin. CONCLUSION: The technique is sure and effective by respecting the indications and the conditions of use.

Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc.

In some patients treated with botulinum toxin (BT), antibodies are produced in association with certain treatment parameters, patient characteristics and immunological properties of the BT preparation used. Therapeutic BT preparations are comprised of botulinum neurotoxin, non-toxic proteins and excipients. Antibodies formed against botulinum neurotoxin can block BT's biological activity. The antigenicity of a BT preparation depends on the amount of botulinum neurotoxin presented to the immune system. This amount is determined by the specific biological activity, the relationship between the biological activity and the amount of botulinum neurotoxin contained in the preparation. For Botox the specific biological activity is 60 MU-EV/ng neurotoxin, for Dysport 100 MU-EV/ng neurotoxin and for Myobloc/NeuroBloc 5 MU-EV/ng neurotoxin. For Myobloc/NeuroBloc this translates into an antibody-induced therapy failure rate of 44% in patients treated for cervical dystonia, whereas for BT type A preparations this figure is approximately 5%. No obvious differences in antigenicity of BT type A preparations have been detected thus far. For the current formulation of Botox, the rate of antibody-induced therapy failure is reportedly less than 1%. To determine the antigenicity of different BT preparations in more detail, prospective studies on large series of unbiased patients with sensitive and specific BT antibody tests are necessary.

Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins.

Botulinum neurotoxins are the most potent toxins designed by nature. They are produced by Clostridium bacteria to cause long-lasting paralysis and death. However, in the past century one member of the botulinum family--botulinum neurotoxin type A--has been put to good use, and is now widely employed in clinical neurology and, even more often, in beauty clinics. This article will critically assess the value of individual members of the botulinum family for experimental neuroscience and medicine. The seven botulinum neurotoxins all act by targeting the same vesicle fusion machinery, and yet they cause paralysis of different durations. The distinct behaviors of botulinum neurotoxins will be discussed, with the aim of highlighting advantages and limitations for their future exploitation.

The story of Clostridium botulinum: from food poisoning to Botox.

In the last fifty years, Clostridium botulinum has become notorious for its ability to produce the deadly botulinum neurotoxins. While botulinum toxin A, better known as Botox, is universally recognised by the public as a cosmetic enhancement tool, the botulinum neurotoxins are commonly used off-label for many medical conditions in ophthalmology, neurology and dermatology. The versatility of these botulinum toxins has made Clostridium botulinum one of the most widely known bacterial pathogens in medical history. This article outlines the discovery of botulinum toxins through to their present day applications in medicine.

Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin.

Food-borne botulism probably has accompanied mankind since its beginning. However, we have only few historical sources and documents on food poisoning before the 19th century. Some ancient dietary laws and taboos may reflect some knowledge about the life-threatening consumption of poisoned food. One example of such a dietary taboo is the 10th century edict of Emperor Leo VI of Byzantium in which manufacturing of blood sausages was forbidden. Some ancient case reports on intoxications with Atropa belladonna probably described patients with food-borne botulism, because the combination of dilated pupils and fatal muscle paralysis cannot be attributed to an atropine intoxication. At the end of the 18th century, some well-documented outbreaks of "sausage poisoning" in Southern Germany, especially in Württemberg, prompted early systematic botulinum toxin research. The German poet and district medical officer Justinus Kerner (1786-1862) published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822. Kerner did not succeed in defining the suspected "biological poison" which he called "sausage poison" or "fatty poison." However, he developed the idea of a possible therapeutic use of the toxin. Eighty years after Kerner's work, in 1895, a botulism outbreak after a funeral dinner with smoked ham in the small Belgian village of Ellezelles led to the discovery of the pathogen Clostridium botulinum by Emile Pierre van Ermengem, Professor of bacteriology at the University of Ghent. The bacterium was so called because of its pathological association with the sausages (Latin word for sausage = "botulus") and not-as it was suggested-because of its shape. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz.

History of the clinical use of botulinum toxin A and B.

The history of the cosmetic use of botulinum toxin (BTX) must begin with the clinical use of BTX in humans. This came out of Alan Scott's work, which was initially an attempt to find a nonsurgical treatment for some forms of strabismus. Alan Scott put together the idea of Ed Maumenee to use BTX to affect extraocular muscles, Art Jampolsky's electromyographic control delivery system, and Ed Schantz' work on the purification of BTX.