Combination molecular therapies for type 1 spinal muscular atrophy

Yohei Harada, Vamshi K. Rao, Kapil Arya, Nancy L. Kuntz, Christine J. DiDonato, Galia Napchan-Pomerantz, Amit Agarwal, Vikki Stefans, Masahisa Katsuno, Aravindhan Veerapandiyan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Background: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking. Methods: This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy. Results: Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved. Conclusions: Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy.

Original languageEnglish (US)
Pages (from-to)550-554
Number of pages5
JournalMuscle and Nerve
Volume62
Issue number4
DOIs
StatePublished - Oct 1 2020

Funding

VS has received support for consultation on Duchenne muscular dystrophy from Sarepta. VR has received support for consultation with AveXis, Biogen, Sarepta, and PTC therapeutics. NLK reports personal fees for participation in Medical Advisory Boards for Audentes, AveXis, Biogen, Cytokinetics and Sarepta. MK has received support from Novartis and Biogen. CJD is partially supported by grants from NIH (NINDS R01NS060926 and R21NS103107), Muscular Dystrophy Association (MDA418685) and CureSMA (DID1617 and DID1718). AV has received support for activities with Biogen AveXis, and PTC therapeutics. AV served as investigator for AveXis MAP and serves as investigator for studies at Arkansas Children's Hospital for SMA (Genentech), DMD (NS Pharma, Sarepta, Pfizer), and Myotonic dystrophy (AMO Pharma). AV serves as an associate editor at MedLink. Other authors have no relevant disclosures.

Keywords

  • SMA
  • combine
  • gene therapy
  • nusinersen
  • onasemnogene

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)
  • Cellular and Molecular Neuroscience
  • Physiology

Fingerprint

Dive into the research topics of 'Combination molecular therapies for type 1 spinal muscular atrophy'. Together they form a unique fingerprint.

Cite this