Dataset Information

Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease.

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.

SUBMITTER: Alliegro M

PROVIDER: S-EPMC5159621 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease.

Alliegro Marialuisa M Ferla Rita R Nusco Edoardo E De Leonibus Chiara C Settembre Carmine C Auricchio Alberto A

Molecular therapy : the journal of the American Society of Gene Therapy 20160923 12

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 respo ...[more]

PMID: 27658524

Similar Datasets

Project description:BackgroundLysosomal storage diseases (LSDs) can be treated with intravenous enzyme replacement therapy (ERT). ERT is being administered either in specialized clinics or in the home care setting. Studies indicate that home-based ERT can be considered safe and positively effects patient reported outcomes. Due to the higher level of individual care required by nurses when administering ERT at home, questions arise whether this will result in additional costs for health care systems. Since cost data to the German health care system are currently unavailable, this study aims to assess home care ERT costs of LSD patients.MethodsThe longitudinal study assessed the direct costs of home-based ERT for patients with LSD diseases Fabry, Pompe, Gaucher, and MPS I from 2019 to 2021 on a patient-by-patient basis by evaluating the healthcare documentation. Costs assessed included ERT drug and further administration equipment, time needed to prepare, administer, and post-process the infusion, and travel expenses of nursing staff.ResultsData from 62 patients was analyzed: of these, 29 (46.8%) with Fabry disease, 19 (30.6%) with Pompe disease, 10 (16.1%) with Gaucher disease, and 4 (6.5%) with MPS I. Patients ranged in age from 3 to 79 (mean 40 years); 42% of patients reported comorbidities (19.4% with hypertension, and 10% with heart disease). Mean total ERT-related costs were €369,047 per year across all patients. Approximately 98.5% of these costs were attributable to the infusion therapy and administration itself (€363,880), and approximately 1.5% were attributable to personnel and travel costs. Patients with Pompe disease incurred the highest average annual costs (€483,907) and patients with Fabry disease the lowest (€264,896). Cost differences among underlying LSDs were due primarily to ERT drug costs; the drug infused for Fabry disease costs about half as much as that for Gaucher or for Pompe disease. Despite MPS I patients requiring about twice as many infusions, significantly lower drug costs for this disease resulted in the second lowest total mean costs of all LSD subtypes analyzed.ConclusionAs total costs are almost entirely driven by infusion-related material, especially the ERT drug, moving ERT into the home environment is not expected to increase costs.

Dataset Information

Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease.

Publications

Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets