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Treatment effect of coenzyme Q 10 and an antioxidant cocktail in fibroblasts of patients with Sanfilippo disease
Author(s) -
Matalonga Leslie,
Arias Angela,
Coll María Josep,
GarciaVilloria Judit,
Gort Laura,
Ribes Antonia
Publication year - 2014
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-013-9668-1
Subject(s) - antioxidant , biology , biochemistry , medicine , endocrinology
Coenzyme Q 10 (CoQ 10 ) plays a key role in the exchange of electrons in lysosomal membrane, which contributes to protons’ translocation into the lumen and to the acidification 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 fibroblasts 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 fibroblasts 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 increase 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 glycosaminoglycans accumulation both, after 50 μmol/L CoQ 10 and antioxidant treatment. Fibroblasts responsive to treatment enhanced 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 treatment in some patients.