Improving clinical trial design for Duchenne muscular dystrophy

BMC Neurology

Volumn 15, Issue 1, 2015, Pages

  Merlini, Luciano ^a   Sabatelli, Patrizia ^a,b  

^a RIZZOLI ORTHOPAEDIC INSTITUTE   (Italy)

^b CNR   (Italy)

Author keywords

Clinical trial; Corticosteroid treatment; Duchenne muscular dystrophy; Dystrophin evaluation; Exon skipping; Splice modulation

Indexed keywords

CORTICOSTEROID; DEFLAZACORT; DYSTROPHIN; PLACEBO; PREDNISONE; DRISAPERSEN; OLIGONUCLEOTIDE;

ARTICLE; BECKER MUSCULAR DYSTROPHY; CORTICOSTEROID THERAPY; DRUG EFFECT; DRUG EFFICACY; DUCHENNE MUSCULAR DYSTROPHY; HUMAN; MUSCLE CELL; MUSCLE STRENGTH; NONHUMAN; OUTCOME ASSESSMENT; PROTEIN EXPRESSION; STUDY DESIGN; CLINICAL TRIAL (TOPIC); COMBINATION DRUG THERAPY; DISEASE COURSE; EXON; GENETICS; MALE; METHODOLOGY; MUSCULAR DYSTROPHY, DUCHENNE; PATHOPHYSIOLOGY; PROCEDURES; TOTAL QUALITY MANAGEMENT; TREATMENT OUTCOME; WALKING;

ADRENAL CORTEX HORMONES; CLINICAL TRIALS AS TOPIC; DISEASE PROGRESSION; DRUG THERAPY, COMBINATION; DYSTROPHIN; EXONS; HUMANS; MALE; MUSCLE STRENGTH; MUSCULAR DYSTROPHY, DUCHENNE; OLIGONUCLEOTIDES; QUALITY IMPROVEMENT; RESEARCH DESIGN; TREATMENT OUTCOME; WALKING;

EID: 84940211391     PISSN: None     EISSN: 14712377     Source Type: Journal    
DOI: 10.1186/s12883-015-0408-z     Document Type: Article

References (57)

1. Hoffman EP, McNally EM. Exon-skipping therapy: a roadblock, detour, or bump in the road? Sci Transl Med. 2014;6(230):230fs214.
2. van Deutekom JC, Janson AA, Ginjaar IB, Frankhuizen WS, Aartsma-Rus A, Bremmer-Bout M, et al. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med. 2007;357(26):2677-86.
3. Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, et al. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 2009;8(10):918-28.
4. Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G, et al. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014;13(10):987-96.
5. Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, Heuvelmans N, et al. Systemic administration of PRO051 in Duchenne's muscular dystrophy. New Engl J Med. 2011;364(16):1513-22.
6. Wilton SD, Veedu RN, Fletcher S. The emperor's new dystrophin: finding sense in the noise. Trends Mol Med. 2015;21:417-26.
7. Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet. 2011;378(9791):595-605.
8. Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013;74(5):637-47.
9. Bushby K, Finkel R, Wong B, Barohn R, Campbell C, Comi GP, et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014;50(4):477-87.
10. Finkel RS, Flanigan KM, Wong B, Bonnemann C, Sampson J, Sweeney HL, et al. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS One. 2013;8(12):e81302.
11. Lu QL, Cirak S, Partridge T. What Can We Learn From Clinical Trials of Exon Skipping for DMD? Mol Ther Nucleic Acids. 2014;3:e152.
12. Hoffman EP, Connor EM. Orphan drug development in muscular dystrophy: update on two large clinical trials of dystrophin rescue therapies. Discov Med. 2013;16(89):233-9.
13. Bhagavati S. Questions about efficacy of exon-skipping therapy for duchenne muscular dystrophy. Ann Neurol. 2014;75(2):326-9.
14. Sheridan C. Doubts raised over 'read-through' Duchenne drug mechanism. Nat Biotechnol. 2013;31(9):771-3.
15. Wilton SD, Fletcher S, Flanigan KM. Dystrophin as a therapeutic biomarker: are we ignoring data from the past? Neuromuscul Disord. 2014;24(6):463-6.
16. Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, et al. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. New Engl J Med. 1988;318(21):1363-8.
17. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9(1):77-93.
18. Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, et al. Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history. Muscle Nerve. 1983;6(2):91-103.
19. Connolly AM, Florence JM, Cradock MM, Malkus EC, Schierbecker JR, Siener CA, et al. Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network. Neuromuscul Disord. 2013;23(7):529-39.
20. Mendell JR, Lloyd-Puryear M. Report of MDA muscle disease symposium on newborn screening for Duchenne muscular dystrophy. Muscle Nerve. 2013;48(1):21-6.
21. Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment Guidance for Industry [ http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM450229.pdf ]
22. Wang RT, Silverstein Fadlon CA, Ulm JW, Jankovic I, Eskin A, et al. Online self-report data for duchenne muscular dystrophy confirms natural history and can be used to assess for therapeutic benefits. PLoS Curr. 2014, 6. doi: 10.1371/currents.md.e1e8f2be7c949f9ffe81ec6fca1cce6a .
23. Cambridge W, Drennan JC. Scoliosis associated with Duchenne muscular dystrophy. J Pediatr Orthop. 1987;7(4):436-40.
24. Gayraud J, Ramonatxo M, Rivier F, Humberclaude V, Petrof B, Matecki S. Ventilatory parameters and maximal respiratory pressure changes with age in Duchenne muscular dystrophy patients. Pediatr Pulmonol. 2010;45(6):552-9.
25. Ishikawa Y, Miura T, Ishikawa Y, Aoyagi T, Ogata H, Hamada S, et al. Duchenne muscular dystrophy: survival by cardio-respiratory interventions. Neuromuscul Disord. 2011;21(1):47-51.
26. Emery AEH. Duchenne muscular dystrophy. Oxford; New York: Oxford University Press; 1987.
27. Zatz M, Rapaport D, Vainzof M, Passos-Bueno MR, Bortolini ER, Pavanello Rde C, et al. Serum creatine-kinase (CK) and pyruvate-kinase (PK) activities in Duchenne (DMD) as compared with Becker (BMD) muscular dystrophy. J Neurol Sci. 1991;102(2):190-6.
28. Merlini L. A 19-year-old ambulant Duchenne patient with stunted growth on long-term corticosteroids. Neuromuscul Disord. 2014;24:417-8.
29. Dubowitz V. A colour atlas of muscle disorders in childhood. London, England: Wolfe Medical Publications; 1989.
30. Drachman DB, Toyka KV, Myer E. Prednisone in Duchenne muscular dystrophy. Lancet. 1974;2(7894):1409-12.
31. Moxley 3rd RT, Pandya S, Ciafaloni E, Fox DJ, Campbell K. Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. J Child Neurol. 2010;25(9):1116-29.
32. Sansome A, Royston P, Dubowitz V. Steroids in Duchenne muscular dystrophy; pilot study of a new low-dosage schedule. Neuromuscul Disord. 1993;3(5-6):567-9.
33. Carter GT, McDonald CM. Preserving function in Duchenne dystrophy with long-term pulse prednisone therapy. Am J Phys Med Rehabil. 2000;79(5):455-8.
34. Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002;12(10):917-25.
35. Merlini L, Gennari M, Malaspina E, Cecconi I, Armaroli A, Gnudi S, et al. Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up. Muscle Nerve. 2012;45(6):796-802.
36. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010;9(2):177-89.
37. Balaban B, Matthews DJ, Clayton GH, Carry T. Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect. Am J Phys Med Rehabil. 2005;84(11):843-50.
38. Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006;16(4):249-55.
39. Daftary AS, Crisanti M, Kalra M, Wong B, Amin R. Effect of long-term steroids on cough efficiency and respiratory muscle strength in patients with Duchenne muscular dystrophy. Pediatrics. 2007;119(2):e320-324.
40. Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, et al. The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures. Muscle Nerve. 2013;48(1):55-67.
41. King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, et al. Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology. 2007;68(19):1607-13.
42. Lebel DE, Corston JA, McAdam LC, Biggar WD, Alman BA. Glucocorticoid treatment for the prevention of scoliosis in children with Duchenne muscular dystrophy: long-term follow-up. J Bone Joint Surg Am. 2013;95(12):1057-61.
43. McAdam LC, Mayo AL, Alman BA, Biggar WD. The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy. Acta Myol. 2012;31(1):16-20.
44. Sanzarello I, Merlini L, Traina F, Rosa MA, Faldini C. Corticosteroid treatment impact on spinal deformity in Duchenne Muscular Dystrophy. International Scholarly Research Notices. 2014;2014:9.
45. Peay HL, Tibben A, Fisher T, Brenna E, Biesecker BB. Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy. Clin Trials. 2014;11(1):77-85.
46. WMA Clarifies Its Ethical Guidance On The Use Of Placebo-Controlled Trials [ http://www.wma.net/en/40news/20archives/2001/2001_05/ ]
47. Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, et al. Early prednisone treatment in Duchenne muscular dystrophy. Muscle Nerve. 2003;27(2):222-7.
48. Houde S, Filiatrault M, Fournier A, Dube J, D'Arcy S, Berube D, et al. Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol. 2008;38(3):200-6.
49. Parreira SL, Resende MB, Zanoteli E, Carvalho MS, Marie SK, Reed UC. Comparison of motor strength and function in patients with Duchenne muscular dystrophy with or without steroid therapy. Arq Neuropsiquiatr. 2010;68(5):683-8.
50. Lynn S, Aartsma-Rus A, Bushby K, Furlong P, Goemans N, De Luca A, et al. Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy. Neuromuscul Disord. 2015;25(1):96-105.
51. van den Bergen JC, van Westrum SM S, Dekker L, van der Kooi AJ, de Visser M, Wokke BH, et al. Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy. J Neurol Neurosurg Psychiatry. 2014;85(1):92-8.
52. den Enden AT H-v, Straathof CS, Aartsma-Rus A, den Dunnen JT, Verbist BM, Bakker E, et al. Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients. Neuromuscul Disord. 2010;20(4):251-4.
53. Pellegrini C, Zulian A, Gualandi F, Manzati E, Merlini L, Michelini ME, et al. Melanocytes--a novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy. J Cell Physiol. 2013;228(6):1323-31.
54. Brown KJ, Marathi R, Fiorillo AA, Ciccimaro EF, Sharma S, Rowlands DS, et al. Accurate Quantitation of Dystrophin Protein in Human Skeletal Muscle Using Mass Spectrometry. J Bioanal Biomed 2012, Suppl 7.
55. Anthony K, Cirak S, Torelli S, Tasca G, Feng L, Arechavala-Gomeza V, et al. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. Brain. 2011;134(Pt 12):3547-59.
56. Arechavala-Gomeza V, Kinali M, Feng L, Brown SC, Sewry C, Morgan JE, et al. Immunohistological intensity measurements as a tool to assess sarcolemma-associated protein expression. Neuropathol Appl Neurobiol. 2010;36(4):265-74.
57. Taylor LE, Kaminoh YJ, Rodesch CK, Flanigan KM. Quantification of dystrophin immunofluorescence in dystrophinopathy muscle specimens. Neuropathol Appl Neurobiol. 2012;38(6):591-601.