Why Dysport®? Dysport is a simple, effective, non-surgical treatment that works by relaxing facial muscles on the forehead, thereby reducing and smoothing away frown-lines and wrinkles. Dysport is supported by over a decade of clinical experience. Dysport was developed in the United Kingdom in the early 1990s to successfully treat a number of neurological and ophthalmic conditions. Since that time, with an increased understanding of the uses of Dysport, thousands of treatments have been safely and effectively performed for a variety of conditions ranging from frown lines to axillary hyperhidrosis (excessive sweating under the armpits). In New Zealand, Dysport has been used for many years, by eye specialists and neurologists, to treat nervous tics and muscle spasms of the face and neck. In fact, Dysport has been available in New Zealand for over 12 years for treating neuro-muscular conditions and was the first botulinum toxin Type A to be approved in New Zealand for medical use. Dysport is manufactured in Britain by Ipsen Limited.

1. INTRODUCTION TO THE COSMETIC USES OF DYSPORT by Dr. Patrick Treacy Medical Director Ailesbury Clinic Dublin Ireland

4. Cosmetic Use of Dysport 1.Horizontal forehead lines 2. Glabellar frown lines 3. Lateral canthal lines 4. Temporal brow lift 5. Upper lips 6. Nasolabial folds 7. Horizontal neck lines 8. Vertical neck lines

5. Botulinum neurotoxin Botulinum toxin (BTX) is produced by a gram-positive anaerobic bacterium Clostridium botulinum , The clinical syndrome of botulism can occur following ingestion of contaminated food, from colonisation of the infant gastrointestinal tract, or from a wound infection. Botulinum toxin is broken into 7 neurotoxins ( types A, B, C [C1, C2], D, E, F, and G ), which are antigenically and serologically distinct but structurally similar. Human botulism is mainly due to types A, B, E, and, rarely, F,G. Types C and D cause toxicity only in animals.

6. Botulinum Toxin Molecule The botulinum toxin molecule is synthesized as a single chain (150 kDa) It is cleaved to form a dichain molecule with a disulfide bridge. The light chain (~50 kDa) acts as a zinc (Zn2+) endopeptidase similar to tetanus toxin The heavy chain (~100 kDa) provides cholinergic specificity and binding of the toxin to presynaptic receptors,

8. New Century 1900 Chemical warfare brought new means of killing people

9. Ypres April 22 nd 1915 5,000 died on the first day and another 5,000 on the second

10. 1916 British chemical warfare complex 7000 acres of scrubland in Porton Down Wiltshire

11. Dublin 1916

12. Porton Down Research Centre Research experiments on Botulinum by Dr. Paul Fides gave rise to DysPORT

13. Porton Down is still active today

14. First victim of experiments Aircraftman Ronald Madison died in May 1953

15. Reinhard Heydrich Assassinated by Czech agents in Prague on 27 th May 1942

16. 1953 US built Fort Detrick Experiments by Edward Schantz gave rise to Botox

21. USE OF DYSPORT COSMETICALLY

22. PATIENT FIVE DAYS LATER

23. FDA approved uses of BTX-A 1. Cervical dystonia 2. Blepharospasm 3. Cranial nerve 11 disorders 4. Facial spasm 5. Glabellar frown lines

27. How muscles contract At a normal neuromuscular junction, a nerve impulse triggers the release of acetylcholine , which causes the muscles to contract. Excessive release of acetylcholine at the neuromuscular junction causes overactive contraction of corrugator and procerus muscle, which over time can cause wrinkles to form.

28. Mechanism of action of BTX-A Botulinum toxin acts by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect. This mechanism laid the foundation for the development of the toxin as a therapeutic tool.

31. Mechanism of BLOCKING of BTX-A The 50-kDa light chain of BTX-A inhibits acetylcholine release by cleaving SNAP-2 (a cytoplasmic protein) SNAP-2 is required for the docking of acetylcholine vesicles on the inner side of the nerve terminal plasma membrane.

32. How muscles contract

34. Mechanism of unBLOCKING of BTX-A The clinical effect of botulinum toxin injections lasts 2-6 months and then resolves After several months, the inactivated terminals slowly recover function, and the new sprouts and end plates regress

35. RESOLUTION of the CLINCIAL EFFECT of BTX-A Clinical effect lasts about 2-6 months and then resolves Recovery occurs through proximal axonal sprouting and muscle reinnervation by formation of new neuromuscular junction. A recent study by De Paiva suggests that, eventually, regeneration of the original neuromuscular junction takes place.

36. BOTULINUM-A TOXIN formulations Dysport ® is another formulation of BTX-A made in England and available in Europe. It is distributed in 500-unit vials that can be stored at room temperature Dysport ® is produced by Speywood Pharmaceuticals in England (Dysport) DYSPORT ® The relative potency of Botox® units to Dysport ® units is approximately 1:4 .

37. Contraindications to Dysport injections Treat patients with diseases of the neuromuscular junction (eg, myasthenia gravis) cautiously because underlying generalized weakness can be exacerbated, and local weakness at injection sites can occur more than otherwise expected