COQ-iPSC

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.