Aggiornamento
Distrofia muscolare di Duchenne:
stato dell’arte su nuovi approcci terapeutici
Duchenne muscular dystrophy: state of the art on new therapeutic approaches
Sonia Messina1, Eugenio Mercuri2
1Dipartimento di Medicina Clinica e Sperimentale, Università di Messina; Centro Clinico Nemo Sud per le malattie neuromuscolari, Policlinico Universitario di Messina
2Istituto di Neuropsichiatria Infantile; Centro Clinico Nemo, Policlinico A. Gemelli, Roma
Novembre 2016 - pagg. 565 -571
Abstract
Duchenne muscular dystrophy is an X-linked disorder with an incidence of 1 in 5,000
male live births and is the most common muscular dystrophy in childhood. The disease is
characterized by progression of muscle weakness and contractures leading to loss of
ambulation before 13 years of age. The heart and respiratory muscle involvement are
the main factors responsible for the limitation of life expectancy. In the last few years the
optimization of the standards of care has produced a progressive increase in survival.
These aspects are even more important at this time when new therapies are entering the
clinical practice. The article reports an update on new therapy development.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Contenuto riservato
Per leggere l'articolo completo è necessario effettuare il login.
Non sei ancora registrato? Registrati
Bibliografia
1. Moat SJ, Bradley DM, Salmon R, Clarke A,
Hartley L. Newborn bloodspot screening for
Duchenne Muscular Dystrophy: 21 years experience
in Wales (UK). Eur J Hum Genet
2013;21(10):1049-53.
2. Passamano L, Taglia A, Palladino A, et al.
Improvement of survival in Duchenne Muscular
Dystrophy: retrospective analysis of
835 patients. Acta Myol 2012;31:121-5.
3. Bushby K, Finkel R, Birnkrant DJ, et al.
Diagnosis and management of Duchenne
muscular dystrophy. Part 1: Diagnosis, and
pharmacological and psychosocial management.
Lancet Neurol 2010;9:77-93.
4. Bushby K, Finkel R, Birnkrant DJ, et al.
Diagnosis and management of Duchenne muscular
dystrophy. Part 2: Implementation of
multidisciplinary care. Lancet Neurol 2010;
9:177-89.
5. Sejerson T, Bushby K; TREAT-NMD EU
Network of Excellence. Standards of care for
Duchenne muscular dystrophy: brief TREAT
NMD recommendations. Adv Exp Med Biol
2009;652:13-21.
6. Finder JD, Birnkrant D, Carl J, et al. Respiratory
care of the patient with Duchenne muscular
dystrophy: ATS consensus statement.
Am J Respir Crit Care Med 2004;170:456-65.
7. Duboc D, Meune C, Lerebours G, Devaux
JY, Vaksmann G, Bécane HM. Effect of perindopril
on the onset and progression of left ventricular
dysfunction in Duchenne muscular dystrophy.
J Am Coll Cardiol 2005;15:855-7.
8. Duboc D, Meune C, Pierre B, et al. Perindopril
preventive treatment on mortality in
Duchenne muscular dystrophy: 10 years’ follow-
up. Am Heart J 2007;154:596-602.
9. Buyse GM, Goemans N, van den Hauwe
M, et al. Idebenone as a novel, therapeutic
approach for Duchenne muscular dystrophy:
results from a 12 month, double- blind, randomized
placebo-controlled trial. Neuromuscul
Disord 2011;21:396-405.
10. Asai A, Sahani N, Kaneki M, Ouchi Y,
Martyn JA, Yasuhara SE. Primary role of
functional ischemia, quantitative evidence for
the two-hit mechanism, and phosphodiesterase-
5 inhibitor therapy in mouse muscular
dystrophy. PLoS One 2007;29:e806.
11. Adamo CM, Dai DF, Percival JM, et al.
Sildenafil reverses cardiac dysfunction in the
mdx mouse model of Duchenne muscular
dystrophy. Proc Natl Acad Sci USA 2010;107:
19079-83.
12. Buckner JL, Bowden SA, Mahan JD. Optimizing
Bone Health in Duchenne Muscular
Dystrophy. Int J Endocrinol 2015;2015: 928385.
13. Rufo A, Del Fattore A, Capulli M, et al.
Mechanisms inducing low bone density in
Duchenne muscular dystrophy in mice and
humans. J Bone Miner Res 2011;8:1891-903.
14. Bianchi ML, Cimaz R, Bardare M, et al. Efficacy
and safety of alendronate for the treatment
of osteoporosis in diffuse connective tissue
diseases in children: a prospective multicenter
study. Arthritis Rheum 2000;43: 1960-6.
15. Leung DG, Germain-Lee EL, Denger BE,
Wagner KR. Report on the Second Endocrine
Aspects of Duchenne Muscular Dystrophy
Conference December 1-2, 2010, Baltimore,
Maryland, USA. Neuromuscul Disord
2011;21:594-601.
16. Gordon KE, Dooley JM, Sheppard KM,
MacSween J, Esser MJ. Impact of bisphosphonates
on sur vival for patients with Duchenne
muscular dystrophy. Pediatrics 2011;
127:353-8.
17. Malik V, Rodino-Klapac LR, Mendell JR,
et al. Emerging drugs for Duchenne muscular
dystrophy. Expert Opin Emerg Drugs
2012;17:261-77.
18. Foster H, Popplewell L, Dickson G. Genetic
therapeutic approaches for Duchenne muscular
dystrophy. Hum Gene Ther 2012;23:
676-87.
19. Konieczny P, Swiderski K, Chamberlain JS.
Gene and cell-mediated therapies for muscular
dystrophy. Muscle Nerve 2013;47:649-63.
20. Malhotra S, Hart K, Klamut H, et al. Frame-
shift deletions in patients with Duchenne
and Becker muscular dystrophy. Science
1988;242:755-9.
21. Chen HC, Cheng SC. Functional roles of
protein splicing factors. Biosci Rep 2012;32:
345-59.
22. Goemans NM, Tulinius M, van den
Akker JT, et al. Systemic administration of
PRO051 in Duchenne’s muscular dystrophy.
N Engl J Med 2011;364:1513-22.
23. Mendell JR, Goemans N, Lowes LP, et al.;
Eteplirsen Study Group and Telethon Foundation
DMD Italian Network. Longitudinal
effect of eteplirsen versus historical control
on ambulation in Duchenne muscular dystrophy.
Ann Neurol 2016;79:257-71.
24. Hoffman EP, Connor EM. Orphan drug
development in muscular dystrophy: Update
on two large clinical trials of dystrophin rescue
therapies. Discov Med 2013;16:233-9.
25. Wein N, Vulin A, Falzarano MS, et al.
Translation from a DMD exon 5 IRES results
in a functional dystrophin isoform that attenuates
dystrophinopathy in humans and mice.
Nat Med 2014;20(9):992-1000.
26. Gurvich OL, Maiti B, Weiss RB, Aggarwal
G, Howard MT, Flanigan KM. DMD
exon 1 truncating point mutations: amelioration
of phenotype by alternative translation
initiation in exon 6. Hum Mutat 2009;30(4):
633-40.
27. Malik V, Rodino-Klapac LR, Viollet L, et
al. Gentamicin-induced readthrough of stop
codons in Duchenne muscular dystrophy.
Ann Neurol 2010;67:771-80.
28. Welch EM, Barton ER, Zhuo J, et al.
PTC124 targets genetic disorders caused by
nonsense mutations. Nature 2007;447:87-91.
29. Bushby K, Finkel R, Wong B, et al.;
PTC124-GD-007-DMD Study Group. Ataluren
treatment of patients with nonsense mutation
dystrophinopathy. Muscle Nerve 2014;
50(4):477-87.
30. McDonald CM, Bushby K, Tulinius M, et
al. Ataluren: an overview of clinical trial results
in nonsense mutation Duchenne Muscular
Dystrophy. 5th International Congress
of Myology, 14-18 March 2016, Lyon, France.
Abstract book P08-149, p. 94.
31. Mendell JR, Campbell K, Rodino-Klapac L,
et al. Dystrophin immunity in Duchenne’s muscular
dystrophy. N Engl J Med 2010;363:
1429-37.
32. Sampaolesi M, Blot S, D’Antona G, et al.
Mesoangioblast stem cells ameliorate muscle
function in dystrophic dogs. Nature 2006;
444:574-9.
33. Tinsley J, Deconinck N, Fisher R, et al.
Expression of full-length utrophin prevents
muscular dystrophy in mdx mice. Nat Med
1998;4:1441-4.
34. Tinsley J, Robinson N, Davies KE. Safety,
tolerability, and pharmacokinetics of SMT
C1100, a 2-arylbenzoxazole utrophin modulator,
following single- and multiple-dose administration
to healthy male adult volunteers. J
Clin Pharmacol 2015;55(6):698-707.
35. Messina S, Bitto A, Aguennouz M, et al.
Nuclear factor kappa-B blockade reduces
skeletal muscle degeneration and enhances
muscle function in Mdx mice. Exp Neurol
2006;198:234-41.
36. Mendell JR, Moxley RT, Griggs RC, et al.
Randomized, double-blind six-month trial of
prednisone in Duchenne’s muscular dystrophy.
N Engl J Med 1989;320:1592-7.
37. Mesa LE, Dubrovsky AL, Corderi J, Marco
P, Flores D. Steroids in Duchenne muscular
dystrophy-deflazacort trial. Neuromuscul
Disord 1991;1:261-6.
38. Mercuri E, Muntoni F. Efficacy of idebenone
in Duchenne muscular dystrophy. Lancet
2015;385(9979):1704-6.
39. Dorchies OM, Wagner S, Vuadens O, et
al. Green tea extract and its major polyphenol
(-)-epigallocatechin gallate improve muscle
function in a mouse model for Duchenne
muscular dystrophy. Am J Physiol Cell Physiol
2006;290:C616-C625.
40. Messina S, Bitto A, Aguennouz M, et al.
Flavocoxid counteracts muscle necrosis and
improves functional properties in mdx mice:
a comparison study with methylprednisolone.
Exp Neurol 2009;220:349-58.
41. Consalvi S, Mozzetta C, Bettica P, et al.
Preclinical studies in the mdx mouse model
of duchenne muscular dystrophy with the histone
deacetylase inhibitor givinostat. Mol
Med 2013;19:79-87.
42. Messina S, Bitto A, Vita GL, et al. Modulation
of neuronal nitric oxide synthase and
apoptosis by the isoflavone genistein in Mdx
mice. Biofactors 2015;41(5):324-9.
43. Wagner KR, McPherron AC, Winik N,
Lee SJ. Loss of myostatin attenuates severity
of muscular dystrophy in mdx mice. Ann
Neurol 2002;52:832-6.
Corrispondenza: emercuri@gmail.com