Thromsø November 2007 Jes Rahbek MD Phd The danish RehabilitationCenter for Neuromuskular Diseases

Inhabitants 5.000.000 Kingdom from 930 p.c.

Jes Rahbek M.D. Rehabilitation RCfM – Rehabiliterings-Center for Muskelsvind

- all of them rare neuromuscular diseases Diagnosis groups DMD Duchenne Muscular Dystrophy BMD Becker Muscular Dystrophy LG Limb girdle FSH Facio-Scapulo-Humeral Dystrophy SMA 1-2-3 Spinal Muscular Atrophy 1-2-3 CM Congenital Myopathy MD Myotonic Dystrophy MG Myasthenia Gravis ALS/MND Amyotrophic Lateral Sclerosis/Motor Neuron Disease - all of them rare neuromuscular diseases

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Hospitaler med neurologisk afd. Neurologi/neuropædiatri 16 sygehuse med specialviden om neuromuskulære sygdomme

DMD population in Denmark Epidemiology Incidence: 7 Prevalence 1977: 80 2003: 150 2010: ?

Description

Hvem drejer rehabilitering sig om Thromsø 2007

The Rehabilitation Centre for Neuromuscular Diseases Government funded, national, multidisciplinary rehabilitation centre (1992) Related to the patient association Muskelsvindfonden (1976) 136 diagnoses, 2000 patients registered (1. January 2007)

FUNKTIONEL REHABILITERING I DANMARK Hospital Hjemme - neurolog Læger: - neurofysiolog Praktiserende læger - respiratorlæge Praktiserende fysiot. Hjemmesygepl. Psykolog Hjemmehjælpere Fysioterapeut Patient og pårørende Ergoterapeut Ergoterapeuter Institut for Socialrådgivere Socialrådgiver Muskelsvind Familie Sygeplejerske Venner Talepædagog Arbejdskolleger Diætist Sygehjælper Sekretær +mange andre Thromsø 2007

Neuromuskulær-rehabilitering Thromsø 2007

Progress in diagnostics and treatment in Neuromuscular Disorders   1862 ALS 1895 SMA 1886 CMT (1a) 1967 Centronucl. myopathy 1932 Pompe 1918 Myotonic dystrophy 1965 Emery Dreifuss 1980 LG (2D) 1885 FSH 1860 Duchenne/ Becker Diagnosis: Cure Medical trials Animal exp. Animal models Prot. function Gene product Variation of gene Gene-isolation Gene-localisation Epidemiology Diagnostic criteria Description Progress in diagnostics and treatment in Neuromuscular Disorders

Enzym replacement terapy Pompe disease OVERVIEW Pompe Disease: History Pompe disease was first described in 1932 by the Dutch pathologist J.C. Pompe. He documented the case of a 7-month-old girl who died suddenly from cardiac hypertrophy.1 Pompe made the important observation that massive amounts of glycogen were present within vacuoles in cardiac muscle as well as in other tissues.2 In 1954, G.T. Cori identified the existence of a class of diseases caused by impaired glycogen metabolism and designated Pompe disease as Glycogen Storage Disease, type II (GSD-II).3 In 1963, H.G. Hers recognized Pompe disease as a lysosomal storage disease after documenting several cases with GAA deficiency.4 Pompe disease was the first of almost 40 lysosomal storage diseases to be described.2 Between 1961 and 1970, several investigators reported a late-onset form of the disease.5-7 The first clinical use of purified human placental GAA was reported in 1973. Several problems hindered the use of placental GAA, including its low-uptake and the limitations in clinical trial design (trial duration and amount of GAA administered).2 In 1979, the gene responsible for Pompe disease was traced to chromosome 17, which provided the basis for further understanding of the pathophysiology and genetics of this disorder.2 Subsequent cloning of the GAA gene made it feasible to produce recombinant human GAA (rhGAA). Clinical trials investigating the efficacy of rhGAA in Pompe disease were initiated in 1999 and are still ongoing.8 References Pompe JC. Over idiopatische hypertrophie van het hart. Ned Tijdschr Geneeskd. 1932;76:304-312. Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:3389-3420. Cori GT. Glycogen structure and enzyme deficiencies in glycogen storage disease. Harvey Lect. 1954;8:145-171. Hers HG. Alpha-glucosidase deficiency in generalized glycogen-storage disease (Pompe’s disease). Biochem J. 1963;86:11-16. Hudgson P, Gardner-Medwin D, Worsfold M, et al. Adult myopathy from glycogen storage disease due to acid maltase deficiency. Brain. 1968;91:435-462. Engel AG. Acid maltase deficiency in adults: studies in four cases of a syndrome which may mimic muscular dystrophy or other myopathies. Brain. 1970;93:599-616. Stoeckle H, Goldman AS, Webb JA. Generalized glycogenosis. Am J Cardiol. 1961;8:675-681. Reuser AJJ, van den Hout H, Bijvoet AGA, et al. Enzyme therapy for Pompe disease: from science to industrial enterprise. Eur J Pediatr. 2002;161:S106-S111. Cori GT. Harvey Lect. 1954;8:145-171. Engel AG. Brain. 1970;93:599-616. Hers HG. Biochem J. 1963;86:11-16. Hirschhorn R, et al. In: The Metabolic and Molecular Bases of Inherited Disease. 2001:3389-3420. Hudgson P, et al. Brain. 1968;91:435-462. Pompe JC. Ned Tijdschr Geneeskd. 1932;76:304-312. Reuser AJJ, et al. Eur J Pediatr. 2002;161:S106-S111. Stoeckle H, et al. Am J Cardiol. 1961;8:675-681.

Muskelsvindfonden Copenhagen 2006 - 100.000 Impairment - disability - handicap Impairment - activity - participation

ICF

Engineering mini - genes

Utrophin upregulation in DMD

Genetherapy

Oligonucleotide-mediated gene editing for neuromuscular disorders

Progress in rehabilitation of people with Neuromuscular Disorders   ALS SMA Duchenne/ Becker 2004 2002 1993 1988 1987 1986 1982 1980 1978 1977 1976 1971 Medical treatment Communication Ambulation Assistive ventilation Scoliosis surgery Adapted homes Adapted wheel-chairs CPAP-treatment Psycology/school Spinal bracing Physiotherapy Education of patients Progress in rehabilitation of people with Neuromuscular Disorders in Denmark