Joint Transnational Call 2012 (JTC2012)


Coenzyme Q10 (CoQ10) is a vital molecule for cell homeostasis. Deficiency of CoQ10 syndrome originates from mutations in genes responsible for CoQsynthesis. CoQ10 deficiency leads to a disorder which manifests with encephalomyopathies, because the disruption of the energy metabolism affects tissues such as cerebellum and skeletal muscle. Many COQ genes have been implicated in the primary CoQ10 deficiency, making the molecular diagnosis and clinical heterogeneity a challenge. To date, there is not a clear association between the mutations and the patients clinical phenotype, and the only current treatment is CoQ10 supplementation which effectiveness remains poor. We propose to generate and differentiate induces pluripotent stem cells from CoQ-deficient patients, before and after correction of the genetic defect, to elucidate the pathogenesis and developmental mechanisms of primary CoQ10 deficiency. Our goals are:(i) study the lack of association between the mutations and the patients clinical phenotype by differentiating COQ-iPSC towards disease-affected tissues (purkinje neurons and skeletal muscle), and (ii) characterize the metabolic dysfunction of iPSC and the differentiated progeny to assess whether exogenous CoQ10 rescues metabolic homeostasis and influences differentiation of COQ-iPSC. We envision these studies will provide novel insights into the genotype-phenotype association and metabolic dysfunction in CoQdeficiency patients.

  • Menendez, Pablo (Coordinator)
    Genomic Oncology Area, Fundación Publica Andaluz y salud Centre for Genomics and Oncology Research [SPAIN]
  • Carriere-Pazat, Audrey
  • Hanna, Jacob
    Department of Molecular Genetics Laboratory for Pluripotent Cell studies The Weizmann Institute of Science Rehovot [ITALY]