Impaired muscle mitochondrial biogenesis and myogenesis in spinal muscular atrophy

Michela Ripolone, Dario Ronchi, Raffaella Violano, Dionis Vallejo, Gigliola Fagiolari, Emanuele Barca, Valeria Lucchini, Irene Colombo, Luisa Villa, Angela Berardinelli, Umberto Balottin, Lucia Morandi, Marina Mora, Andreina Bordoni, Francesco Fortunato, Stefania Corti, Daniela Parisi, Antonio Toscano, Monica Sciacco, Salvatore Di MauroGiacomo P. Comi, Maurizio Moggio

Research output: Contribution to journalArticlepeer-review


IMPORTANCE: The important depletion of mitochondrial DNA (mtDNA) and the general depression of mitochondrial respiratory chain complex levels (including complex II) have been confirmed, implying an increasing paucity of mitochondria in the muscle from patients with types I, II, and III spinal muscular atrophy (SMA-I, -II, and-III, respectively). OBJECTIVE: To investigate mitochondrial dysfunction in a large series of muscle biopsy samples from patients with SMA. DESIGN, SETTING, AND PARTICIPANTS: We studied quadriceps muscle samples from 24 patients with genetically documented SMA and paraspinal muscle samples from 3 patients with SMA-II undergoing surgery for scoliosis correction. Postmortem muscle samples were obtained from 1 additional patient. Age-matched controls consisted of muscle biopsy specimens from healthy children aged 1 to 3 years who had undergone analysis for suspected myopathy. Analyses were performed at the Neuromuscular Unit, Istituto di Ricovero e Cura a Carattere Scientifico Foundation Ca' Granda Ospedale Maggiore Policlinico-Milano, from April 2011 through January 2015. EXPOSURES: We used histochemical, biochemical, and molecular techniques to examine the muscle samples. MAIN OUTCOMES AND MEASURES: Respiratory chain activity and mitochondrial content. RESULTS: Results of histochemical analysis revealed that cytochrome-c oxidase (COX) deficiency was more evident in muscle samples from patients with SMA-I and SMA-II. Residual activities for complexes I, II, and IV in muscles from patients with SMA-I were 41%, 27%, and 30%, respectively, compared with control samples (P

Original languageEnglish
Pages (from-to)666-675
Number of pages10
JournalJAMA Neurology
Issue number6
Publication statusPublished - Jun 1 2015

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


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