ORIGINAL ARTICLE Treatment effect of coenzyme Q 10 and an antioxidant cocktail in fibroblasts of patients with Sanfilippo disease Leslie Matalonga & Angela Arias & María Josep Coll & Judit Garcia-Villoria & Laura Gort & Antonia Ribes Received: 7 August 2013 /Revised: 30 October 2013 /Accepted: 26 November 2013 # SSIEM and Springer Science+Business Media Dordrecht 2013 Abstract Coenzyme Q 10 (CoQ 10 ) plays a key role in the exchange of electrons in lysosomal membrane, which contrib- utes to protons’ translocation into the lumen and to the acid- ification of intra-lysosomal medium, which is essential for the proteolytic function of hydrolases responsible -when deficient- of a wide range of inherited lysosomal diseases such as Sanfilippo syndromes. Our aim was to evaluate whether treatment with CoQ 10 or with an antioxidant cocktail (α- tocopherol, N-acetylcysteine and α-lipoic acid) were able to ameliorate the biochemical phenotype in cultured fibroblasts of Sanfilippo patients. Basal CoQ 10 was analyzed in fibro- blasts and Sanfilippo A patients showed decreased basal levels. However, no dysfunction in the CoQ 10 biosynthesis pathways was found, revealing for the first time a secondary CoQ 10 deficiency in Sanfilippo A fibroblasts. Cultured fibro- blasts from five patients affected by Sanfilippo A and B diseases were treated with CoQ 10 and an antioxidant cocktail. Upon CoQ 10 treatment, none of the Sanfilippo A fibroblasts increased their residual enzymatic activity, but the two Sanfilippo B cell lines showed a statistically significant in- crease of their residual activity. The antioxidant treatment had no effect on the residual activity in all tested cell lines. Moreover, one Sanfilippo A and two Sanfilippo B fibroblasts showed a statistically significant reduction of glycosamino- glycans accumulation both, after 50 μmol/L CoQ 10 and anti- oxidant treatment. Fibroblasts responsive to treatment en- hanced their exocytosis levels. Our results are encouraging as some cellular alterations observed in Sanfilippo syndrome can be partially restored by CoQ 10 or other antioxidant treat- ment in some patients. Introduction Coenzyme Q 10 (CoQ 10 ) is a lipophilic molecule synthesized in all cells (no dietary uptake is required) and is present in all membranes in eukaryotic organisms. The best known function is its role as electron carrier in the mitochondrial respiratory chain. However, more functions are attributed to CoQ 10 and it is currently known that it participates in a great number of metabolic processes such as prevention of lipid, protein and DNA oxidation; regulation of mitochondrial uncoupling pro- teins; formation of mitochondrial permeability transition pores; pyrimidine nucleoside biosynthesis and apoptosis (Turunen et al 2004). Although CoQ 10 has a prominent role in the mitochondrial respiratory chain by transporting electrons from complex I and complex II to complex III, both the lysosomal and mitochon- drial membranes contain similar proportions of CoQ 10 (Turunen et al 2004). In fact, several studies have shown that CoQ 10 also plays a key role in the exchange of electrons in the lysosomal membrane, which contributes to protons’ translo- cation into the lumen and to the acidification of the intra- lysosomal medium (Gille and Nohl 2000). Acidification is essential for the proteolytic function of intra-lysosomal hydro- lases since these enzymes require acid pH for optimal activi- ties. As it occurs in the mitochondrial respiratory chain, oxy- gen is the final electron acceptor in the lysosomal electron transport chain and can potentially trigger the onset of reactive Communicated by: Ron A. Wevers Electronic supplementary material The online version of this article (doi:10.1007/s10545-013-9668-1) contains supplementary material, which is available to authorized users. L. Matalonga : A. Arias : M. J. Coll : J. Garcia-Villoria : L. Gort : A. Ribes (*) Secció d’Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, CIBER de Enfermedades Raras (CIBERER), Edifici Helios III, planta baixa, C/Mejía Lequerica s/n, 08028 Barcelona, Spain e-mail: aribes@clinic.ub.es J Inherit Metab Dis DOI 10.1007/s10545-013-9668-1