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

The Lancet Neurology

Volumn 16, Issue 7, 2017, Pages 513-522

  Bertini, Enrico ^a   Dessaud, Eric ^b   Mercuri, Eugenio ^c   Muntoni, Francesco ^d   Kirschner, Janbernd ^e   Reid, Carol ^f   Lusakowska, Anna ^g   Comi, Giacomo P ^h   Cuisset, Jean Marie ⁱ   Abitbol, Jean Louis ^b   Scherrer, Bruno ^j   Ducray, Patricia Sanwald ^k   Buchbjerg, Jeppe ^k   Vianna, Eduardo ^k   van der Pol, W Ludo ^l   Vuillerot, Carole ^m   Blaettler, Thomas ^k   Fontoura, Paulo ^k   André, Carole ⁿ   Bruno, Claudio ⁿ   Chabrol, Brigitte ⁿ   Deconinck, Nicolas ⁿ   Estournet, Brigitte ⁿ   Fontaine Carbonnel, Stephanie ⁿ   Goemans, Nathalie ⁿ   Gorni, Ksenija ⁿ   Govoni, Alessandra ⁿ   Guglieri, Michela ⁿ   Lochmuller, Hanns ⁿ   Magri, Francesca ⁿ   Mayer, Michele ⁿ   Müller Felber, Wolfgang ⁿ   Rivier, François ⁿ   Roper, Helen ⁿ   Schara, Ulrike ⁿ   Scoto, Mariacristina ⁿ   van den Berg, Leonard ⁿ   Vita, Giuseppe ⁿ   Walter, Maggie C ⁿ   more..

^a BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^b Trophos   (France)

^c FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

^e UNIVERSITY OF FREIBURG   (Germany)

^f ROCHE PRODUCTS LTD   (United Kingdom)

^g MEDICAL UNIVERSITY OF WARSAW   (Poland)

^h UNIVERSITY OF MILAN   (Italy)

ⁱ LILLE UNIVERSITY HOSPITAL   (France)

^j Bruno Scherrer Conseil   (France)

^k F HOFFMANN LA ROCHE LTD   (Switzerland)

^l UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^m HOSPICES CIVILS DE LYON   (France)

ⁿ Centre Hospitalier Universitaire de Lyon ^*

more..

Author keywords

[No Author keywords available]

Indexed keywords

OLESOXIME; CHOLEST 4 EN 3 ONE; NEUROPROTECTIVE AGENT;

ADOLESCENT; ADULT; ARTICLE; BELGIUM; CHILD; CONTROLLED STUDY; COUGHING; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FATALITY; FEMALE; FEVER; FRANCE; GERMANY; HUMAN; ITALY; MAJOR CLINICAL STUDY; MALE; MOTOR PERFORMANCE; MULTICENTER STUDY; NETHERLANDS; PHASE 2 CLINICAL TRIAL; POLAND; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SPINAL MUSCULAR ATROPHY; UNITED KINGDOM; VOMITING; CLINICAL TRIAL; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PRESCHOOL CHILD; SPINAL MUSCULAR ATROPHIES OF CHILDHOOD; WALKING DIFFICULTY; YOUNG ADULT;

ADOLESCENT; ADULT; CHILD; CHILD, PRESCHOOL; CHOLESTENONES; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MOBILITY LIMITATION; NEUROPROTECTIVE AGENTS; OUTCOME ASSESSMENT (HEALTH CARE); SPINAL MUSCULAR ATROPHIES OF CHILDHOOD; YOUNG ADULT;

EID: 85018331440     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(17)30085-6     Document Type: Article

References (29)

1. Lunn, MR, Wang, CH, Spinal muscular atrophy. Lancet 371 (2008), 2120–2133.
2. Crawford, TO, Pardo, CA, The neurobiology of childhood spinal muscular atrophy. Neurobiol Dis 3 (1996), 97–110.
3. Qian, Y, McGraw, S, Henne, J, Jarecki, J, Hobby, K, Yeh, WS, Understanding the experiences and needs of individuals with Spinal Muscular Atrophy and their parents: a qualitative study. BMC Neurol, 15, 2015, 217.
4. Lefebvre, S, Burlet, P, Liu, Q, et al. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16 (1997), 265–269.
5. Acsadi, G, Lee, I, Li, X, et al. Mitochondrial dysfunction in a neural cell model of spinal muscular atrophy. J Neurosci Res 87 (2009), 2748–2756.
6. Katsetos, CD, Koutzaki, S, Melvin, JJ, Mitochondrial dysfunction in neuromuscular disorders. Semin Pediatr Neurol 20 (2013), 202–215.
7. Ripolone, M, Ronchi, D, Violano, R, et al. Impaired muscle mitochondrial biogenesis and myogenesis in spinal muscular atrophy. JAMA Neurol 72 (2015), 666–675.
8. Miller, N, Shi, H, Zelikovich, AS, Ma, YC, Motor neuron mitochondrial dysfunction in spinal muscular atrophy. Hum Mol Genet 25 (2016), 3395–3406.
9. Shababi, M, Lorson, CL, Rudnik-Schoneborn, SS, Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease?. J Anat 224 (2014), 15–28.
10. Procaccio, V, Bris, C, Chao de la Barca, JM, et al. Perspectives of drug-based neuroprotection targeting mitochondria. Rev Neurol (Paris) 170 (2014), 390–400.
11. US Food and Drug Administration. Prescribing Information SPINRAZA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209531lbl.pdf (accessed Jan 30, 2017).
12. Gabanella, F, Carissimi, C, Usiello, A, Pellizzoni, L, The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Hum Mol Genet 14 (2005), 3629–3642.
13. Bordet, T, Berna, P, Abitbol, JL, Pruss, RM, Olesoxime (TRO19622): a novel mitochondrial-targeted neuroprotective compound. Pharmaceuticals 3 (2010), 345–368.
14. Gouarne, C, Giraudon-Paoli, M, Seimandi, M, et al. Olesoxime protects embryonic cortical neurons from camptothecin intoxication by a mechanism distinct from BDNF. Br J Pharmacol 168 (2013), 1975–1988.
15. Gouarne, C, Tracz, J, Paoli, MG, et al. Protective role of olesoxime against wild-type alpha-synuclein-induced toxicity in human neuronally differentiated SHSY-5Y cells. Br J Pharmacol 172 (2015), 235–245.
16. Bordet, T, Buisson, B, Michaud, M, et al. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther 322 (2007), 709–720.
17. Estournet, B, Chabrol, B, Cuisset, J, et al. Safety and pharmacokinetics (PK) of TRO19622 in spinal muscular atrophy (SMA) children and adults. Neurology, 72(suppl 3), 2009, A276.
18. Lenglet, T, Lacomblez, L, Abitbol, JL, et al. A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis. Eur J Neurol 21 (2014), 529–536.
19. Berard, C, Payan, C, Hodgkinson, I, Fermanian, J, MFM Collaborative Study Group. A motor function measure for neuromuscular diseases. Construction and validation study. Neuromuscul Disord 15 (2005), 463–470.
20. de Lattre, C, Payan, C, Vuillerot, C, et al. Motor function measure: validation of a short form for young children with neuromuscular diseases. Arch Phys Med Rehabil 94 (2013), 2218–2226.
21. Iannaccone, ST, Hynan, LS, Morton, A, Buchanan, R, Limbers, CA, Varni, JW, for the AmSMART Group. The PedsQL in pediatric patients with spinal muscular atrophy: feasibility, reliability, and validity of the Pediatric Quality of Life Inventory Generic Core Scales and Neuromuscular Module. Neuromuscul Disord 19 (2009), 805–812.
22. Vuillerot, C, Payan, C, Iwaz, J, Ecochard, R, Berard, C, for the MFM Spinal Muscular Atrophy Study Group. Responsiveness of the motor function measure in patients with spinal muscular atrophy. Arch Phys Med Rehabil 94 (2013), 1555–1561.
23. Crawford, TO, Concerns about the design of clinical trials for spinal muscular atrophy. Neuromuscul Disord 14 (2004), 456–460.
24. Mercuri, E, Finkel, R, Montes, J, et al. Patterns of disease progression in type 2 and 3 SMA: implications for clinical trials. Neuromuscul Disord 26 (2016), 126–131.
25. Iannaccone, ST, Browne, RH, Samaha, FJ, Buncher, CR, Prospective study of spinal muscular atrophy before age 6 years. DCN/SMA Group. Pediatr Neurol 9 (1993), 187–193.
26. Mazzone, E, De Sanctis, R, Fanelli, L, et al. Hammersmith Functional Motor Scale and Motor Function Measure-20 in non ambulant SMA patients. Neuromuscul Disord 24 (2014), 347–352.
27. Kang, PB, Gooch, CL, McDermott, MP, et al. The motor neuron response to SMN1 deficiency in spinal muscular atrophy. Muscle Nerve 49 (2014), 636–644.
28. Schneider, LS, Raman, R, Schmitt, FA, et al. Characteristics and performance of a modified version of the ADCS-CGIC CIBIC+ for mild cognitive impairment clinical trials. Alzheimer Dis Assoc Disord 23 (2010), 260–267.
29. CureSMA. The Voices of SMA: the experiences of individuals and families and their views on living with spinal muscular atrophy. http://www.curesma.org/documents/research-documents/voices-of-sma-booklet.pdf (accessed Sept 22, 2016).