Gene Therapy for Lysosomal Storage Disorders

Gonzalez, Esteban Alberto; Baldo, Guilherme

doi:10.1177/2326409816689786

Cited by 7 publications

(3 citation statements)

References 44 publications

(65 reference statements)

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“…Therefore, various AAV serotypes have been developed with particular tropism for cells and tissues of interest, including neurons and glia, and tested in pre-clinical mouse models of LSDs (Bailey et al, 2018). AAV-mediated GT successfully improved the phenotypes of GM1 gangliosidosis, MPS I & IIIB, Sandhoff disease, metachromatic leukodystrophy, and Krabbe disease (Gonzalez and Baldo, 2017). Based on the positive results from these animal models, multiple phase I/II clinical trials are currently being conducted, many of which have promising results.…”

Section: Gene Therapymentioning

confidence: 99%

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

Favret

Weinstock

Feltri

et al. 2020

Front. Mol. Biosci.

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There are over 50 lysosomal hydrolase deficiencies, many of which cause neurodegeneration, cognitive decline and death. In recent years, a number of broad innovative therapies have been proposed and investigated for lysosomal storage diseases (LSDs), such as enzyme replacement, substrate reduction, pharmacologic chaperones, stem cell transplantation, and various forms of gene therapy. Murine models that accurately reflect the phenotypes observed in human LSDs are critical for the development, assessment and implementation of novel translational therapies. The goal of this review is to summarize the neurodegenerative murine LSD models available that recapitulate human disease, and the pre-clinical studies previously conducted. We also describe some limitations and difficulties in working with mouse models of neurodegenerative LSDs.

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Section: Gene Therapymentioning

confidence: 99%

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

Favret

Weinstock

Feltri

et al. 2020

Front. Mol. Biosci.

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“…There are two gene therapy approaches for brain involvement in LDs. In one case, the vector carrying the therapeutic gene is administered in vivo, either by in situ administration or by an intravenous injection of a vector with a tropism for brain cells [71,86]. The latter can also be used for other LDs without brain involvement by targeting the vector to other organs [87].…”

Section: Gene Therapy/genome Editingmentioning

confidence: 99%

Precision Medicine for Lysosomal Disorders

et al. 2020

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Precision medicine (PM) is an emerging approach for disease treatment and prevention that accounts for the individual variability in the genes, environment, and lifestyle of each person. Lysosomal diseases (LDs) are a group of genetic metabolic disorders that include approximately 70 monogenic conditions caused by a defect in lysosomal function. LDs may result from primary lysosomal enzyme deficiencies or impairments in membrane-associated proteins, lysosomal enzyme activators, or modifiers that affect lysosomal function. LDs are heterogeneous disorders, and the phenotype of the affected individual depends on the type of substrate and where it accumulates, which may be impacted by the type of genetic change and residual enzymatic activity. LDs are individually rare, with a combined incidence of approximately 1:4000 individuals. Specific therapies are already available for several LDs, and many more are in development. Early identification may enable disease course prediction and a specific intervention, which is very important for clinical outcome. Driven by advances in omics technology, PM aims to provide the most appropriate management for each patient based on the disease susceptibility or treatment response predictions for specific subgroups. In this review, we focused on the emerging diagnostic technologies that may help to optimize the management of each LD patient and the therapeutic options available, as well as in clinical developments that enable customized approaches to be selected for each subject, according to the principles of PM.

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“…This means that not all cells need to be corrected, as long as the distribution of the enzyme is efficient. Therefore, LDs are considered good targets for gene therapy, despite their multisystem involvement (Gonzalez and Baldo, 2017).…”

Section: Considerations About Treatmentmentioning

confidence: 99%

Lysosomal diseases: Overview on current diagnosis and treatment

et al. 2019

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Lysosomal diseases (LDs), also known as lysosomal storage diseases (LSDs), are a heterogeneous group of conditions caused by defects in lysosomal function. LDs may result from deficiency of lysosomal hydrolases, membrane-associated transporters or other non-enzymatic proteins. Interest in the LD field is growing each year, as more conditions are, or will soon be treatable. In this article, we review the diagnosis of LDs, from clinical suspicion and screening tests to the identification of enzyme or protein deficiencies and molecular genetic diagnosis. We also cover the treatment approaches that are currently available or in development, including hematopoietic stem cell transplantation, enzyme replacement therapy, small molecules, and gene therapy.

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Gene Therapy for Lysosomal Storage Disorders

Cited by 7 publications

References 44 publications

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

Precision Medicine for Lysosomal Disorders

Lysosomal diseases: Overview on current diagnosis and treatment

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