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

doi:10.1002/mus.27034

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

Pediatrics

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	550-554
Number of pages	5
Journal	Muscle and Nerve
Volume	62
Issue number	4
DOIs	https://doi.org/10.1002/mus.27034
State	Published - 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

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10.1002/mus.27034

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title = "Combination molecular therapies for type 1 spinal muscular atrophy",

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.",

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author = "Yohei Harada and Rao, \{Vamshi K.\} and Kapil Arya and Kuntz, \{Nancy L.\} and DiDonato, \{Christine J.\} and Galia Napchan-Pomerantz and Amit Agarwal and Vikki Stefans and Masahisa Katsuno and Aravindhan Veerapandiyan",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC",

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doi = "10.1002/mus.27034",

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AU - Harada, Yohei

AU - Rao, Vamshi K.

AU - Arya, Kapil

AU - Kuntz, Nancy L.

AU - DiDonato, Christine J.

AU - Napchan-Pomerantz, Galia

AU - Agarwal, Amit

AU - Stefans, Vikki

AU - Katsuno, Masahisa

AU - Veerapandiyan, Aravindhan

N1 - Funding Information: 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. Publisher Copyright: © 2020 Wiley Periodicals LLC

PY - 2020/10/1

Y1 - 2020/10/1

N2 - 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.

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Combination molecular therapies for type 1 spinal muscular atrophy

Abstract

Funding

Keywords

ASJC Scopus subject areas

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