α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice

Pharmaceutics

Ana Alarcia-Lacalle¹  MaríaÁngeles Solinís Aspiazu¹  Alicia Rodríguez-Gascón¹  Itziar Gómez-Aguado¹  Ana del Pozo-Rodríguez¹  Julen Rodríguez-Castejón¹  Mónica Vicente-Pascual¹ 

[1] Pharmacokinetic, Nanotechnology and Gene Therapy Group (Pharma Nano Gene), Centro de Investigación Lascaray Ikergunea, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain;

关键词: gene therapy;    non-viral vectors;    solid lipid nanoparticles;    pDNA;    Fabry disease;    Fabry mice;   

DOI  :  10.3390/pharmaceutics13060771

来源: DOAJ

【 摘 要 】

Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.

【 授权许可】

Unknown