Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1)

Martina G.L. Perego, Noemi Galli, Monica Nizzardo, Alessandra Govoni, Michela Taiana, Nereo Bresolin, Giacomo P. Comi, Stefania Corti

Research output: Contribution to journalReview article

Abstract

Spinal muscular atrophy (SMA) with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease that is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory distress. Without intervention, infants with the severe form of the disease die before 2 years of age. SMARD1 is caused by mutations in the IGHMBP2 gene that determine a deficiency in the encoded IGHMBP2 protein, which plays a critical role in motor neuron survival because of its functions in mRNA processing and maturation. Although it is rare, SMARD1 is the second most common motor neuron disease of infancy, and currently, treatment is primarily supportive. No effective therapy is available for this devastating disease, although multidisciplinary care has been an essential element of the improved quality of life and life span extension in these patients in recent years. The objectives of this review are to discuss the current understanding of SMARD1 through a summary of the presently known information regarding its clinical presentation and pathogenesis and to discuss emerging therapeutic approaches. Advances in clinical care management have significantly extended the lives of individuals affected by SMARD1 and research into the molecular mechanisms that lead to the disease has identified potential strategies for intervention that target the underlying causes of SMARD1. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to halt or possibly prevent neurodegenerative disease in SMARD1 patients. The recent approval of the first gene therapy approach for SMA associated with mutations in the SMN1 gene may be a turning point for the application of this strategy for SMARD1 and other genetic neurological diseases.

Original languageEnglish
Pages (from-to)3351-3367
JournalCellular and Molecular Life Sciences
Volume77
Issue number17
DOIs
Publication statusPublished - 2020

Keywords

  • Distal hereditary motor neuropathy type 6
  • Gene therapy
  • IGHMBP2
  • Motor neuron disease
  • Oligonucleotides
  • SMARD1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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