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Current Treatment Options in Neurology

Erschienen in:

01.06.2019 | Neuromuscular Disorders (C Fournier, Section Editor)

Current Treatment Options in Neurology—SMA Therapeutics

verfasst von: Megan A. Waldrop, MD, Stephen J. Kolb, MD, PhD

Erschienen in: Current Treatment Options in Neurology | Ausgabe 6/2019

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Abstract

Purpose of review

In this review, we discuss the clinical and genetic features of 5q spinal muscular atrophy and highlight approved and upcoming therapies.

Recent findings

We emphasize that multidisciplinary care has been a key component of the improved quality and length of life seen in these individuals in the past decade. We discuss the evidence leading to the approval of nusinersen and the evidence leading to the anticipated approval of onasemnogene abeparvovec-xioi. Additional clinical therapies that are on the horizon are discussed and the importance of continued multidisciplinary care even after treatment is emphasized.

Summary

The pursuit of therapies for spinal muscular atrophy is becoming a success story and continued development of biomarkers will allow for more informed therapeutic decision making and eventual cost-effective utilization of available therapies.

Pearn JH. The gene frequency of acute Werdnig-Hoffmann disease (SMA type 1). A total population survey in North-East England. J Med Genet. 1973;10(3):260–5.CrossRef

Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012;20(1):27–32. https://doi.org/10.1038/ejhg.2011.134.CrossRefPubMed

Beattie CE, Kolb SJ. Spinal muscular atrophy: selective motor neuron loss and global defect in the assembly of ribonucleoproteins. Brain Res. 2018;1693(Pt A:92–7. https://doi.org/10.1016/j.brainres.2018.02.022.CrossRefPubMed

4.•

Kolb SJ, Coffey CS, Yankey JW, Krosschell K, Arnold WD, Rutkove SB, et al. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol. 2017;82(6):883–91. https://doi.org/10.1002/ana.25101. A longitudinal, prospective description of the natural history of type 1 spinal muscular atrophy.CrossRef

Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155–65.CrossRef

Zerres K, Rudnik-Schoneborn 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(5):518–23.CrossRef

Russman BS. Spinal muscular atrophy: clinical classification and disease heterogeneity. J Child Neurol. 2007;22(8):946–51. https://doi.org/10.1177/0883073807305673.CrossRefPubMed

Munsat TL, Skerry L, Korf B, Pober B, Schapira Y, Gascon GG, et al. Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2-13.3 (SMA 5q). Neurology. 1990;40(12):1831–6.CrossRef

Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002;4(1):20–6. https://doi.org/10.1097/00125817-200201000-00004.CrossRef

10.

Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, et al. A positive modifier of spinal muscular atrophy in the SMN2 gene. Am J Hum Genet. 2009;85(3):408–13. https://doi.org/10.1016/j.ajhg.2009.08.002.CrossRefPubMedPubMedCentral

11.

CureSMA. New York to implement newborn screening for SMA October 1st. 2018.

12.

Glascock J, Sampson J, Haidet-Phillips A, Connolly A, Darras B, Day J, et al. Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening. J Neuromuscul Dis. 2018;5(2):145–58. https://doi.org/10.3233/JND-180304.CrossRefPubMedPubMedCentral

13.

Kolb SJ, Kissel JT. Spinal muscular atrophy: a timely review. Arch Neurol. 2011;68(8):979–84. https://doi.org/10.1001/archneurol.2011.74.CrossRefPubMed

14.

Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, et al. Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018;28(3):197–207. https://doi.org/10.1016/j.nmd.2017.11.004.CrossRefPubMed

15.

Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, et al. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103–15. https://doi.org/10.1016/j.nmd.2017.11.005.CrossRefPubMed

16.

Finkel RS, McDermott MP, Kaufmann P, Darras BT, Chung WK, Sproule DM, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83(9):810–7. https://doi.org/10.1212/WNL.0000000000000741.CrossRefPubMedPubMedCentral

17.

Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017–26. https://doi.org/10.1016/S0140-6736(16)31408-8.CrossRefPubMed

18.••

Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377(18):1723–32. https://doi.org/10.1056/NEJMoa1702752. Prospective, randomized, double-blind study showing the efficacy of nusinersen for the treatment of type 1 spinal muscular atrophy.CrossRef

19.

Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625–35. https://doi.org/10.1056/NEJMoa1710504.CrossRefPubMed

20.

Chiriboga CA, Swoboda KJ, Darras BT, Iannaccone ST, Montes J, De Vivo DC, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology. 2016;86(10):890–7. https://doi.org/10.1212/WNL.0000000000002445.CrossRefPubMedPubMedCentral

21.

Bielsky AR, Fuhr PG, Parsons JA, Yaster M. A retrospective cohort study of children with spinal muscular atrophy type 2 receiving anesthesia for intrathecal administration of nusinersen. Paediatr Anaesth. 2018;28(12):1105–8. https://doi.org/10.1111/pan.13500.CrossRefPubMed

22.

Sansone VA, Albamonte E, Salmin F, Casiraghi J, Pirola A, Bettinelli M, et al. Intrathecal nusinersen treatment for SMA in a dedicated neuromuscular clinic: an example of multidisciplinary and integrated care. Neurol Sci. 2018;40:327–32. https://doi.org/10.1007/s10072-018-3622-9.CrossRefPubMed

23.

Wurster CD, Winter B, Wollinsky K, Ludolph AC, Uzelac Z, Witzel S, et al. Intrathecal administration of nusinersen in adolescent and adult SMA type 2 and 3 patients. J Neurol. 2018;266:183–94. https://doi.org/10.1007/s00415-018-9124-0.CrossRefPubMed

24.

Schuster DJ, Dykstra JA, Riedl MS, Kitto KF, Belur LR, McIvor RS, et al. Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front Neuroanat. 2014;8:42. https://doi.org/10.3389/fnana.2014.00042.CrossRefPubMedPubMedCentral

25.

Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, et al. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010;28(3):271–4. https://doi.org/10.1038/nbt.1610.CrossRefPubMedPubMedCentral

26.

Duque SI, Arnold WD, Odermatt P, Li X, Porensky PN, Schmelzer L, et al. A large animal model of spinal muscular atrophy and correction of phenotype. Ann Neurol. 2015;77(3):399–414. https://doi.org/10.1002/ana.24332.CrossRefPubMedPubMedCentral

27.

Meyer K, Ferraiuolo L, Schmelzer L, Braun L, McGovern V, Likhite S, et al. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther. 2015;23(3):477–87. https://doi.org/10.1038/mt.2014.210.CrossRefPubMed

28.••

Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377(18):1713–22. https://doi.org/10.1056/NEJMoa1706198. Prospective study showing the safety and efficacy of gene replacement therapy in type 1 spinal muscular atrophy.CrossRef

29.

Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2018. https://doi.org/10.1002/ppul.24203.

30.

Ayuso E, Blouin V, Lock M, McGorray S, Leon X, Alvira MR, et al. Manufacturing and characterization of a recombinant adeno-associated virus type 8 reference standard material. Hum Gene Ther. 2014;25(11):977–87. https://doi.org/10.1089/hum.2014.057.CrossRefPubMedPubMedCentral

31.

Naryshkin NA, Weetall M, Dakka A, Narasimhan J, Zhao X, Feng Z, et al. Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science. 2014;345(6197):688–93. https://doi.org/10.1126/science.1250127.CrossRefPubMed

32.

Sivaramakrishnan M, McCarthy KD, Campagne S, Huber S, Meier S, Augustin A, et al. Binding to SMN2 pre- mRNA-protein complex elicits specificity for small molecule splicing modifiers. Nat Commun. 2017;8(1):1476. https://doi.org/10.1038/s41467-017-01559-4.CrossRefPubMedPubMedCentral

33.

Palacino J, Swalley SE, Song C, Cheung AK, Shu L, Zhang X, et al. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Nat Chem Biol. 2015;11(7):511–7. https://doi.org/10.1038/nchembio.1837.CrossRefPubMed

34.

F. Hoffman-La Roche P. Update on clinical development of RG7800. 2015.

35.

Novartis. Novartis Releases Update on LMI070 (Branaplam) Clinical Trial. 2017.

36.

Bordet T, Berna P, Abitbol JL, Pruss RM. Olesoxime (TRO19622): a novel mitochondrial-targeted neuroprotective compound. Pharmaceuticals (Basel). 2010;3(2):345–68. https://doi.org/10.3390/ph3020345.CrossRef

37.

Bertini E, Dessaud E, Mercuri E, Muntoni F, Kirschner J, Reid C, 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(7):513–22. https://doi.org/10.1016/S1474-4422(17)30085-6.CrossRefPubMed

38.

Andrews JA, Miller TM, Vijayakumar V, Stoltz R, James JK, Meng L, et al. CK-2127107 amplifies skeletal muscle response to nerve activation in humans. Muscle Nerve. 2018;57(5):729–34. https://doi.org/10.1002/mus.26017.CrossRefPubMed

39.

Yu Y, Zhang P, Han N, Kou Y, Yin X, Jiang B. Collateral development and spinal motor reorganization after nerve injury and repair. Am J Transl Res. 2016;8(7):2897–911.PubMedPubMedCentral

40.

Senol MG, Kaplan C, Ozdag F, Saracoglu M. How long does denervation take in poliomyelitis? Or is it a lifetime? J Neurosci Rural Pract. 2017;8(4):511–5. https://doi.org/10.4103/jnrp.jnrp_173_17.CrossRefPubMedPubMedCentral

41.

Kolb SJ, Coffey CS, Yankey JW, Krosschell K, Arnold WD, Rutkove SB, et al. Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. Ann Clin Transl Neurol. 2016;3(2):132–45. https://doi.org/10.1002/acn3.283.CrossRefPubMedPubMedCentral

42.

Arnold WD, Rutkove S, Simard L, Kolb SJ. Development and testing of biomarkers in spinal muscular atrophy. In: Sumner CJ, Paushkin S, Ping C-P, editors. Spinal muscular atrophy: disease mechanisms and therapy. San Diego: Academic Press; 2017. p. 383–97.CrossRef

43.

Rossi D, Volanti P, Brambilla L, Colletti T, Spataro R, La Bella V. CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis. J Neurol. 2018;265(3):510–21. https://doi.org/10.1007/s00415-017-8730-6.CrossRef

Titel: Current Treatment Options in Neurology—SMA Therapeutics
verfasst von: Megan A. Waldrop, MD
Stephen J. Kolb, MD, PhD
Publikationsdatum: 01.06.2019
Verlag: Springer US
Erschienen in: Current Treatment Options in Neurology / Ausgabe 6/2019
Print ISSN: 1092-8480
Elektronische ISSN: 1534-3138
DOI: https://doi.org/10.1007/s11940-019-0568-z

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Current Treatment Options in Neurology—SMA Therapeutics

Abstract

Purpose of review

Recent findings

Summary

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Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

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Update Neurologie

Springer Medizin

Abstract

Purpose of review

Recent findings

Summary

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Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie