Spinal Muscular Atrophy Therapeutics

Where do we Stand?

Constantin d’Ydewalle, Charlotte Sumner

Research output: Contribution to journalArticle

Abstract

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder pathologically characterized by the degeneration of motor neurons in the spinal cord and muscle atrophy. Motor neuron loss often results in severe muscle weakness causing affected infants to die before reaching 2 years of age. Patients with milder forms of SMA exhibit slowly progressive muscle weakness over many years. SMA is caused by the loss of SMN1 and the retention of at least 1 copy of a highly homologous SMN2. An alternative splicing event in the pre-mRNA arising from SMN2 results in the production of low levels of functional SMN protein. To date, there are no effective treatments available to treat patients with SMA. However, over the last 2 decades, the development of SMA mouse models and the identification of therapeutic targets have resulted in a promising drug pipeline for SMA. Here, we highlight some of the therapeutic strategies that have been developed to activate SMN2 expression, modulate splicing of the SMN2 pre-mRNA, or replace SMN1 by gene therapy. After 2 decades of translational research, we now stand within reach of a treatment for SMA.

Original languageEnglish (US)
Pages (from-to)303-316
Number of pages14
JournalNeurotherapeutics
Volume12
Issue number2
DOIs
StatePublished - Apr 1 2015

Fingerprint

Spinal Muscular Atrophy
RNA Precursors
Muscle Weakness
Motor Neurons
Therapeutics
Translational Medical Research
Muscular Atrophy
Alternative Splicing
Genetic Therapy
Spinal Cord
Pharmaceutical Preparations

Keywords

  • Gene activation
  • Gene therapy
  • Spinal muscular atrophy
  • Splicing modulation
  • Survival motor neuron

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Clinical Neurology
  • Pharmacology

Cite this

Spinal Muscular Atrophy Therapeutics : Where do we Stand? / d’Ydewalle, Constantin; Sumner, Charlotte.

In: Neurotherapeutics, Vol. 12, No. 2, 01.04.2015, p. 303-316.

Research output: Contribution to journalArticle

d’Ydewalle, Constantin ; Sumner, Charlotte. / Spinal Muscular Atrophy Therapeutics : Where do we Stand?. In: Neurotherapeutics. 2015 ; Vol. 12, No. 2. pp. 303-316.
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