Faculty Bibliography

INTRODUCTION/BACKGROUND:Inotersen, an antisense oligonucleotide inhibitor of TTR protein production, demonstrated significant benefit versus placebo in the modified Neuropathy Impairment Score +7 neurophysiologic tests (mNIS+7) in patients with hereditary transthyretin-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 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 deep breathing did not show significant effects. DISCUSSION/CONCLUSIONS:The results of this analysis reinforce the beneficial effect of inotersen on slowing neuropathy progression in patients with hATTR polyneuropathy. This article is protected by copyright. All rights reserved.

INTRODUCTION/BACKGROUND:Hereditary transthyretin-mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO-TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients' neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score. METHODS:Stage 1/2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline, 35, and 66 weeks. RESULTS:At 66 weeks, inotersen-treated patients experienced symptom stabilization versus worsening in patients receiving placebo in NSC total score; the subdomains of muscle weakness, sensory, pain, and autonomic symptoms; and for various individual items. DISCUSSION/CONCLUSIONS:Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR based on the NSC score, which may be an effective assessment of neuropathy progression and patients' neuropathy experience in clinical practice. This article is protected by copyright. All rights reserved.

INTRODUCTION/BACKGROUND:), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. METHODS:) and its subscores and correlation with disability and health scores. RESULTS:sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. CONCLUSIONS:, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901-911, 2017.