Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms

Monica Nizzardo, Martina Nardini, Dario Ronchi, Sabrina Salani, Chiara Donadoni, Francesco Fortunato, Giorgia Colciago, Marianna Falcone, Chiara Simone, Giulietta Riboldi, Alessandra Govoni, Nereo Bresolin, Giacomo P. Comi, Stefania Corti

Research output: Contribution to journalArticle

Abstract

Spinal muscular atrophy (SMA) is a devastating genetic motoneuron disease leading to infant death. No effective therapy is currently available. It has been suggested that β-lactam antibiotics such as ceftriaxone may offer neuroprotection in motoneuron diseases. Here, we investigate the therapeutic effect of ceftriaxone in a murine model of SMA. Treated animals present a modest, but significant ameliorated neuromuscular phenotype and increased survival, which correlate with protection of neuromuscular units. Whole gene expression profiling in treated mice demonstrates modifications in several genes including those involved in RNA metabolism toward wild-type. The neuroprotective effect seems to be mediated by multiple mechanisms that encompass the increase of the glutamate transporter Glt1, the transcription factor Nrf2, as well as SMN protein. This study provides the first evidence of a potential positive effect of this class of molecules in SMA. Further investigation of analogs with increased and more specific therapeutic effects warrants the development of useful therapies for SMA.

Original languageEnglish
Pages (from-to)214-225
Number of pages12
JournalExperimental Neurology
Volume229
Issue number2
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Ceftriaxone
  • Pharmacological treatment
  • Spinal muscular atrophy

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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