The oral splicing modifier RG7800 increases full length survival of motor neuron 2 mRNA and survival of motor neuron protein: Results from trials in healthy adults and patients with spinal muscular atrophy.

Heidemarie Kletzl, Anne Marquet, Andreas Günther, Wakana Tang, Jules Heuberger, Geert Jan Groeneveld, Willem Birkhoff, Eugenio Maria Mercuri, Hanns Lochmüller, Claire Wood, Dirk Fischer, Irene Gerlach, Katja Heinig, Teodorica Bugawan, Sebastian Dziadek, Russell Kinch, Christian Czech, Omar Khwaja

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Abstract Spinal muscular atrophy (SMA) is a rare genetic and progressively debilitating neuromuscular disease. It is the leading genetic cause of death among infants. In SMA, low levels of survival of motor neuron (SMN) protein lead to motor neuron death and muscle atrophy as the SMN protein is critical to motor neuron survival. SMA is caused by mutations in, or deletion of, the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein due to alternative splicing which excludes exon 7 from most transcripts, generating truncated, rapidly degraded SMN protein. Patients with SMA rely on limited expression of functional SMN full-length protein from the SMN2 gene, but insufficient levels are generated. RG7800 is an oral, selective SMN2 splicing modifier designed to modulate alternative splicing of SMN2 to increase the levels of functional SMN protein. In two trials, oral administration of RG7800 increased in blood full-length SMN2 mRNA expression in healthy adults and SMN protein levels in SMA patients by up to two-fold, which is expected to provide clinical benefit. Copyright © 2018 Elsevier B.V. All rights reserved. KEYWORDS: Neuromuscular disease; SMN protein; SMN2 splicing modifier; Spinal muscular atrophy; Survival of motor neuron
Original languageEnglish
Pages (from-to)21-29
Number of pages9
JournalNeuromuscular Disorders
DOIs
Publication statusPublished - 2019

Keywords

  • spinal muscular atrophy.

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