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DOI: 10.1055/s-0038-1635070
Therapie und Monitoring neuromuskulärer Repeat-Erkrankungen
Therapy and monitoring of repeat diseasesPublication History
eingegangen am:
13 September 2016
angenommen am:
05 October 2016
Publication Date:
03 February 2018 (online)
Zusammenfassung
Repeat-Erkrankungen sind hereditäre durch pathologische Expansionen sich wiederholender Triplettoder Multiplett-DNA-Sequenzen (Repeats) hervorgerufene, in der Regel multisystemische Erkrankungen. Bevorzugt das neuromuskuläre System betreffen die myotonen Dystrophien Typ 1 und 2 (DM 1, 2), die okulopharyngeale Muskeldystrophie (OPMD), die spinobulbäre Muskelatrophie (SBMA, auch Kennedy-Syndrom) und eine Form der ALS, die durch Repeat-Expansionen im C9ORF72-Gen verursacht wird. Zunehmendes Verständnis der molekularen Pathogenese dieser Erkrankungen bildet die Grundlage für neue kausale Therapiestrategien, die sich überwiegend noch im präklinischen Stadium befinden oder in ersten klinischen Studien getestet werden. Das Monitoring und die Therapie von neurologischen und internistischen Symptomen (wie respiratorischer Insuffizienz oder kardialer Mitbeteiligung) erfordert eine interdisziplinäre Betreuung.
Summary
Repeat diseases are hereditary often multisystemic disorders caused by pathological expansions of repeated DNA sequences. The neuromuscular system is predominantly affected in myotonic dystrophy type 1 and 2 (DM1 and 2), oculopharyngeal muscular dystrophy (OPMD), spinal and bulbar muscle atrophy (SBMA, Kennedy’s disease) and a variant of amyotrophophic lateral sclerosis (ALS) caused by repeat expansions in the C9ORF72 gene. Increasing knowledge of the molecular pathogenesis has paved the way for novel therapeutic strategies which are currently subject of preclinical and first clinical studies. Monitoring and therapy of neurological and non-neurological symptoms (e.g . respiratory insufficiency or cardiac involvement) often require interdisciplinary treatment.
Schlüsselwörter
Myotone Dystrophie - okulopharyngeale Muskeldystrophie - spinobulbäre Muskelatrophie - ALS - symptomatische Therapie-
Literatur
- 1 Schneider-Gold Kress W, Grimm T, Schoser B. Myotone Dystrophien. Akt Neurologie 2010; 07: 348-59.
- 2 Schneider-Gold C. et al. Creatine monohydrate in DM 2/PROMM. A double blind placebo-controlled clinical study. Neurology 2003; 60: 500-2.
- 3 Walter MC. et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurology 2002; 249: 17171-22.
- 4 Harper PS, van Engelen B, Eymard B, Wilcox DE. (eds.) Myotonic dystrophy: present management, future therapy. Oxford: University Press; 2004
- 5 Logigian EL. et al. Mexuilitine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology 2010; 23: 466-476.
- 6 Groh WJ. et al. Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med 2008; 358: 2688-2693.
- 7 Annane D, Moore DH, Barnes PR, Miller RG. Psychostimulants for hypersomnia excessive daytime sleepiness) in myotonic dystrophy. Cochrane Database Syst Rev 2006; 03: CD003218.
- 8 Raz V, Butler-Browne G, van Engelen B, Brais B. Neurmuscul Disord. 2013; 23: 516-23.
- 9 Chartier A. et al. Mitochondrial dysfunction reveals the role of mRNA Poly(A) tail regulation in oculopharyngeal muscular dystrophy pathogenesis. PLOS Genetics 2015; 11 (03) e1005092.
- 10 Harish P. et al. Progress on gene therapy, cell therapy, and pharmacological strategies towards treatment of oculopharyngeal muscular dystrophy. Hum Gene Ther 2015; 26: 286-92.
- 11 Armon C, Kurland LT, Daube JR, O’Brien PC. Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology 1991; 41 (07) 1077-84.
- 12 Uenal HA. et al. Incidence and geographical variation of amyotrophic lateral sclerosis (ALS) in Southern Germany – completeness of the ALS registry Swabia. PLoS One 2014; 09 (04) e93932.
- 13 Hubers A. et al. [Amyotrophic lateral sclerosis. Multisystem degeneration]. Nervenarzt 2016; 87 (02) 179-88.
- 14 Rosen DR. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362 (6415): 59-62.
- 15 Sreedharan J. et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319 (5870): 1668-72.
- 16 Vance C. et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009; 323 (5918): 1208-11.
- 17 DeJesus-Hernandez M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72 (02) 245-56.
- 18 Woollacott IO, Mead S. The C9ORF72 expansion mutation: gene structure, phenotypic and diagnostic issues. Acta Neuropathol 2014; 127 (03) 319-32.
- 19 Wilke C. et al. Atypical parkinsonism in C9orf72 expansions: a case report and systematic review of 45 cases from the literature. J Neurol 2016; 263 (03) 558-74.
- 20 Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 1994; 330 (09) 585-91.
- 21 Lacomblez L. et al. A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II. Neurology 1996; 47 (6 Suppl 4): S242-S250.
- 22 Lacomblez L. et al. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996; 347 (9013): 1425-31.
- 23 Traynor BJ. et al. An outcome study of riluzole in amyotrophic lateral sclerosis – a population-based study in Ireland, 1996–2000. J Neurol 2003; 250 (04) 473-9.
- 24 Mis MS. et al. Development of therapeutics for C9ORF72 ALS/FTD-related disorders. Mol Neurobiol. 2016 Jun 28; epub.
- 25 Miller TM. et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol 2013; 12 (05) 435-42.
- 26 Andersen PM. et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. Eur J Neurol 2012; 19 (03) 360-75.
- 27 La Spada AR. et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991; 352 (6330): 77-9.
- 28 Katsuno M. et al. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA). Prog Neurobiol 2012; 99 (03) 246-56.
- 29 Kuhlenbaumer G. et al. [X-chromosomal recessive spinobulbar muscular atrophy (Kennedy type). Description of a family, clinical aspects, molecular genetics, differential diagnosis and therapy]. Nervenarzt 1998; 69 (08) 660-5.
- 30 Sperfeld AD. et al. X-linked bulbospinal neuronopathy: Kennedy disease. Arch Neurol 2002; 59 (12) 1921-6.
- 31 Mariotti et al. Phenotypic manifestations associated with CAG-repeat expansion in the androgen receptor gene in male patients and heterozygous females: a clinical and molecular study of 30 families. Neuromuscul Disord 2000; 10 (06) 391-7.
- 32 Li M. et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol 1998; 44 (02) 249-54.
- 33 Rinaldi C, Malik B, Greensmith L. Targeted molecular therapies for SBMA. J Mol Neurosci 2016; 58 (03) 335-42.
- 34 Weydt P. et al. Clinical Trials in Spinal and Bulbar Muscular Atrophy-Past, Present, and Future. J Mol Neurosci 2016; 58 (03) 379-87.