mNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis

P. James B. Dyck, John C. Kincaid, Janice F. Wiesman, Michael Polydefkis, William J. Litchy, Michelle L. Mauermann, Elizabeth J. Ackermann, Spencer Guthrie, Michael Pollock, Shiangtung W. Jung, Brenda F. Baker, Peter J. Dyck

Research output: Contribution to journalArticle

Abstract

Introduction: Inotersen, an antisense oligonucleotide inhibitor of transthyretin (TTR) protein production, demonstrated significant benefit versus placebo in the modified Neuropathy Impairment Score (NIS) +7 neurophysiologic tests (mNIS+7) in patients with hereditary TTR-mediated amyloidosis (hATTR) with polyneuropathy. This analysis assessed the mNIS+7 components by anatomic location and the lower limb function (LLF) test. Methods: Adults with hATTR in the NEURO-TTR trial (NCT01737398) were randomly assigned to receive weekly doses of subcutaneous inotersen 300 mg or placebo for 65 weeks. The mNIS+7 and LLF were assessed at 35 and 66 weeks. Results: All major mNIS+7 components (muscle weakness, muscle stretch reflexes, sensation) and the LLF showed significant efficacy in patients receiving inotersen versus placebo; however, NIS-reflexes (upper limb), touch pressure (upper and lower limbs), and heart rate during deep breathing did not show significant effects. Discussion: The results of this analysis reinforce the beneficial effect of inotersen on slowing neuropathy progression in patients with hATTR polyneuropathy.

Original languageEnglish (US)
JournalMuscle and Nerve
DOIs
StateAccepted/In press - 2020
Externally publishedYes

Keywords

  • amyloidosis
  • hATTR
  • inotersen
  • lower limb function
  • mNIS+7

ASJC Scopus subject areas

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

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  • Cite this

    Dyck, P. J. B., Kincaid, J. C., Wiesman, J. F., Polydefkis, M., Litchy, W. J., Mauermann, M. L., Ackermann, E. J., Guthrie, S., Pollock, M., Jung, S. W., Baker, B. F., & Dyck, P. J. (Accepted/In press). mNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis. Muscle and Nerve. https://doi.org/10.1002/mus.27022