Animals; Central Nervous System Agents/economics/therapeutic use; Drug Approval; Humans; Muscular Atrophy, Spinal/drug therapy/economics; Oligonucleotides/economics/therapeutic use
Résumé :
[en] Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants. The most severe and most common form, type 1 SMA, is associated with early mortality in most cases and severe disability in survivors. Nusinersen, an antisense oligonucleotide, promotes production of full-length protein from the pseudogene SMN2. Nusinersen treatment prolongs survival of patients with type 1 SMA and allows motor milestone acquisition. Patients with type 2 SMA also show progress on different motor scales after nusinersen treatment. Nusinersen was recently approved by the European Medicines Agency and the US Food and Drug Administration; it is now reimbursed in several European countries and in the USA. In Australia, the transition from expanded access programme to commercial availability is coming soon. In New Zealand, an expanded access programme is opened, and in Canada price negotiation for the treatment is in progress. In this review we exemplify the clinical benefit of nusinersen in subgroups of patients with SMA. Nusinersen represents the first efficacious marked approved drug in type 1 and type 2 SMA. Different knowledge gaps, such as results in older patients, in patients with permanent ventilation, in patients with neonatal forms, or in patients after spinal fusion, still need to be addressed. WHAT THIS PAPER ADDS: Identifies gaps in knowledge about the efficacy of nusinersen in broader populations of patients with spinal muscular atrophy. Identifies open questions in populations of patients where proof of efficacy is available.
Disciplines :
Neurologie Pédiatrie
Auteur, co-auteur :
Gidaro, Teresa
Servais, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
Langue du document :
Anglais
Titre :
Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps.
Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review. Orphanet J Rare Dis 2017; 12: 124.
Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995; 80: 155–65.
Lorson CL, Androphy EJ. An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum Mol Genet 2000; 9: 259–65.
Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology 2014; 83: 810–17.
Farrar MA, Vucic S, Johnston HM, du Sart D, Kiernan MC. Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy. J Pediatr 2013; 162: 155–9.
Zerres K, Rudnik-Schöneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 1995; 52: 518–23.
Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord 2018; 28: 103–15.
Singh NK, Singh NN, Androphy EJ, Singh RN. Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron. Mol Cell Biol 2006; 26: 1333–46.
Hua Y, Vickers TA, Okunola HL, Bennett CF, Krainer AR. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet 2008; 82: 834–48.
Porensky PN, Mitrpant C, McGovern VL, et al. A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse. Hum Mol Genet 2012; 21: 1625–38.
Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 2016; 86: 890–7.
Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 2016; 388: 3017–26.
Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med 2017; 377: 1723–32.
Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med 2018; 378: 625–35.
Bertini E, Hwu W-L, Reyna SP, et al. Efficacy and safety of nusinersen in infants with presymptomatic spinal muscular atrophy (SMA): interim results from the NURTURE study. Eur J Paediatr Neurol 2017; 21(Suppl. 1): e14.
Pechmann A, Langer T, Schorling D, et al. Evaluation of children with SMA type 1 under treatment with nusinersen within the expanded access program in Germany. J Neuromuscul Dis 2018; 5: 135–43.
Messina S, Pane M, Sansone V, et al. Expanded access program with nusinersen in SMA type I in Italy: strengths and pitfalls of a successful experience. Neuromuscul Disord 2017; 27: 1084–6.
Aragon-Gawinska K, Daron A, Gargaun E, et al. Nusinersen in spinal muscular atrophy type 1 patients older than 7 months: a cohort study. Neurology 2018; https://doi.org/10.1212/WNL.0000000000006281.
Farrar MA, Teoh HL, Carey KA, et al. Nusinersen for SMA: expanded access programme. J Neurol Neurosurg Psychiat 2018; 89: 937–42.
Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Molec Med 2013; 19: 40–50.
Boardman FK, Young PJ, Griffiths FE. Newborn screening for spinal muscular atrophy: the views of affected families and adults. Am J Med Genet A 2017; 173: 1546–61.
Magri F, Vanoli F, Corti S. miRNA in spinal muscular atrophy pathogenesis and therapy. J Cell Molec Med 2018; 22: 755–67.
Geraci AP, Black K, Jin M, Rimler S, Evans A. Transforaminal lumbar puncture for intrathecal nusinersen administration. Muscle Nerve 2018; https://doi.org/10.1002/mus.26082.
Montes JYD, Mazzone E, Pasternak A, et al. Ambulatory function and fatigue in nusinersen-treated children with spinal muscular atrophy. Muscle Nerve 2018; https://doi.org/10.1002/mus.26082 [Epub ahead of print].
Naryshkin NA, Weetall M, Dakka A, et al. Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science 2014; 345: 688–93.
Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med 2017; 377: 1713–22.
Bertini E, Dessaud E, Mercuri E, et al. Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017; 16: 513–22.
Klug C, Schreiber-Katz O, Thiele S, et al. Disease burden of spinal muscular atrophy in Germany. Orphanet J Rare Dis 2016; 11: 58.
Prasad V. Nusinersen for spinal muscular atrophy: are we paying too much for too little? JAMA Pediatr 2018; 172: 123–5.
Chabanon A, Seferian AM, Daron A, et al. Prospective and longitudinal natural history study of patients with type 2 and 3 spinal muscular atrophy: baseline data NatHis-SMA study. PLoS ONE 2018; 13: e0201004.
