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Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease
- Source :
- Molecular Therapy
- Publication Year :
- 2016
-
Abstract
- Enzyme replacement therapy (ERT) is the standard of care for several lysosomal storage diseases (LSDs). ERT, however, requires multiple and costly administrations and has limited efficacy. We recently showed that a single high dose administration of adeno-associated viral vector serotype 8 (AAV2/8) is at least as effective as weekly ERT in a mouse model of mucopolysaccharidosis type VI (MPS VI). However, systemic administration of high doses of AAV might result in both cell-mediated immune responses and insertional mutagenesis. Here we evaluated whether the combination of low doses of AAV2/8 with a less frequent (monthly) than canonical (weekly) ERT schedule may be as effective as the single treatments at high doses or frequent regimen. A greater reduction of both urinary glycosaminoglycans, considered a sensitive biomarker of therapeutic efficacy, and storage in the myocardium and heart valves was observed in mice receiving the combined than the single therapies. Importantly, these levels of correction were similar to those we obtained in a previous study following either high doses of AAV2/8 or weekly ERT. Our data show that low-dose gene therapy can be used as a means to rarify ERT administration, thus reducing both the risks and costs associated with either therapies.Molecular Therapy (2016); doi:10.1038/mt.2016.181.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Genetic enhancement
Mucopolysaccharidosis type VI
Genetic Vectors
Pharmacology
03 medical and health sciences
Mice
Genetic
Drug Discovery
Lysosomal storage disease
medicine
Genetics
Combined Modality Therapy
Animals
Humans
Enzyme Replacement Therapy
Molecular Biology
Glycosaminoglycans
business.industry
Drug Discovery3003 Pharmaceutical Science
nutritional and metabolic diseases
Enzyme replacement therapy
Genetic Therapy
Dependovirus
medicine.disease
3. Good health
Lysosomal Storage Diseases
Regimen
Disease Models, Animal
030104 developmental biology
Treatment Outcome
Systemic administration
Biomarker (medicine)
Molecular Medicine
Original Article
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....3978c39ae7f7e8107e70eb4d41350312