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.

Development of botulinum toxin therapy.

Justinius Kerner collected data on 230 cases of botulism in the 1820s, suggested the therapeutic use of toxin, and gave a remarkably complete and accurate description of clinical botulism: its symptoms, time course, and the physical findings that the tear fluid disappears, the skin is dry, the eye, gut, and somatic muscles are paralyzed, and mucus and saliva secretion is suppressed. These effects are the clinical targets of botulinum therapy today. Inspired by Drachman's use of toxin to safely paralyze the hind limb in chicks, we worked out the procedures for its safe medical application and licensure from 1972 to 1989, applying it first to correct strabismus, blepharospasm, leg muscle spasm, and torticollis. This list is now extended by others to well over 100 uses. For many years, blepharospasm patients returning for injection around the eyes and upper face would mention as a joke that they were "back to get the wrinkles out." Working in aesthetic dermatology and ophthalmology, Alistair and Jean Carruthers could envision the intentional cosmetic application of botulinum toxin, probably its greatest single use today.

[Botulinum toxin--the dose controls the poison. A historical sketch]. / Botulinumtoxin--Die Dosis macht das Gift. Ein historischer Abriss.

Botulism, a potentially lethal form of paralytic food poisoning, was described as early as 1793. Basic research, especially in the late nineteenth and early twentieth centuries, revealed that botulism is caused by exotoxins. Further biochemical work around and after the Second World War gave insight into the molecular structure of seven different serotypes of botulinum toxin (BT/A-G) as well as into its acetylcholine blocking mode of action. In 1977, Scott treated patients with strabism by injecting minute amounts of purified BT/A. In short sequence, BT proved effective in blepharospasm, cervical dystonia, and various off-label indications. In the near future, registration of these new indications, marketing of new serotypes (BT/B), and availability of more practical antibody tests can be expected. The first applications of BT were performed by Roggenkaemper, Dressler, and Benecke in Germany and by Poewe and Auff in Austria. According to a worldwide trend, a rapid expansion regarding BT users and indications followed. Formation of BT competence centers in both countries aims at maintaining high standards in BT research and education.

Botulinum toxin type A: history and current cosmetic use in the upper face.

This article reviews the cosmetic use of botulinum toxin in upper face from both the historic and clinical viewpoints. The published literature and our current experience are outlined. Botulinum toxin type A in the upper face has become an extremely popular cosmetic procedure and is outstandingly safe.

Botulinum toxin type A: history and current cosmetic use in the upper face.

This article reviews the cosmetic use of botulinum toxin in upper face from both the historic and clinical viewpoints. The published literature and our current experience are outlined. Botulinum toxin type A in the upper face has become an extremely poplular cosmetic procedure and is outstandingly safe.