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

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.

• Authors: 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
• Journal: Muscle & nerve (Muscle Nerve) Vol. 62 Issue 4 Pg. 502-508 (10 2020) ISSN: 1097-4598 [Electronic] United States
• PMID: 32654212 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.

Chemical References

• Oligonucleotides
• Oligonucleotides, Antisense
• Inotersen

Topics

• Amyloid Neuropathies, Familial (drug therapy, physiopathology)
• Double-Blind Method
• Female
• Heart Rate (drug effects)
• Humans
• Lower Extremity (physiopathology)
• Male
• Middle Aged
• Muscle Weakness (drug therapy, physiopathology)
• Oligonucleotides (pharmacology, therapeutic use)
• Oligonucleotides, Antisense (pharmacology, therapeutic use)
• Reflex (drug effects)
• Treatment Outcome