Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease
@article{Stok2020LentiviralHS, title={Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease}, author={Merel Stok and Helen de Boer and Marshall W. Huston and Ed Jacobs and Onno Roovers and Trudi P. Visser and Holger Jahr and Dirk Jan Duncker and Elza D van Deel and Arnold J. J. Reuser and Niek P. van Til and Gerard Wagemaker}, journal={Molecular Therapy. Methods \& Clinical Development}, year={2020}, volume={17}, pages={1014 - 1025} }
21 Citations
Gene Therapy Developments for Pompe Disease
- Medicine, BiologyBiomedicines
- 2022
Pompe disease is an inherited neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The most severe form is infantile-onset Pompe disease, presenting…
Screening chimeric GAA variants in preclinical study results in hematopoietic stem cell gene therapy candidate vectors for Pompe disease
- BiologyMolecular therapy. Methods & clinical development
- 2022
Lentiviral gene therapy prevents anti-human acid α-glucosidase antibody formation in murine Pompe disease
- BiologyMolecular therapy. Methods & clinical development
- 2022
IGF2-tagging of GAA promotes full correction of murine Pompe disease at a clinically relevant dosage of lentiviral gene therapy
- BiologyMolecular therapy. Methods & clinical development
- 2022
Therapeutic thoroughfares for adults living with Pompe disease
- Medicine, BiologyCurrent opinion in neurology
- 2022
Therapy of Pompe disease reaches new thoroughfares reducing the overall disease burden of patients; however, individualization of these novel therapeutic options remains challenging.
Therapeutic Options for the Management of Pompe Disease: Current Challenges and Clinical Evidence in Therapeutics and Clinical Risk Management
- Biology, MedicineTherapeutics and clinical risk management
- 2022
The data obtained from randomized clinical trials but also from open-label studies published so far that have assessed the advantages and limitations of Enzymatic replacement therapy (ERT) are reviewed and the new therapeutic strategies that are under development are reviewed.
Promoter considerations in the design of lentiviral vectors for use in treating lysosomal storage diseases
- BiologyMolecular therapy. Methods & clinical development
- 2022
Stem Cell Applications in Lysosomal Storage Disorders: Progress and Ongoing Challenges.
- BiologyAdvances in experimental medicine and biology
- 2021
An overview of current research data indicates that when stem cell and/or gene therapy applications are used in combination with existing therapies such as ERT, SRT, and chaperone therapies, promising results can be achieved, showing that these treatments may result in alleviation of existing symptoms and/ or prevention of progression of the disease.
Phenotypic implications of pathogenic variant types in Pompe disease
- Medicine, BiologyJournal of Human Genetics
- 2021
It is found that multiple types of splice site variants beyond the classic c.−32–13T > G variant are often associated with a milder phenotype, and enzyme activity levels continue to have utility for supporting the diagnosis when the genetic variants are ambiguous.
Genetically engineered microglia-like cells have therapeutic potential for neurodegenerative disease
- BiologybioRxiv
- 2021
It is demonstrated in murine models of Parkinson’s disease and frontotemporal dementia that MLCs can provide therapeutically relevant levels of protein to the brain, thereby potentially opening avenues of HSPC-GT to address the underlying disease etiology of these and other similar disorders.
References
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It is concluded that ex vivo HSC gene therapy is a treatment option worthwhile to pursue on the basis of the prominent and sustained therapeutic efficacy without adverse events in mice.
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Pompe disease is a rare autosomal recessive metabolic disorder caused by defi ciency of lysosomal hydrolase acid α-glucosidase, and generalized tissue glycogen accumulation leading to cardiorespiratory failure in the early-onset patients within the first year of life.
Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance.
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AAV vector-mediated gene therapy induced a tolerance to introduced GAA, and this strategy could enhance the efficacy of ERT in CRIM-negative patients with Pompe disease and in patients with other lysosomal storage diseases.
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It is shown that LV-mediated delivery system was effective in correcting the biochemical abnormalities and that this gene transfer system might be suitable for further studies on delivering GAA to Pompe disease mouse models.
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A neuron-specific gene therapy improved the motor coordination of Pompe mice by lowering glycogen accumulation, decreasing astrogliosis, and increasing myelination, indicating that neurological deficits are responsible for a significant burden in Pompe disease.
Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy
- Medicine, BiologyScience
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The reconstitution of ARSA activity in the cerebrospinal fluid and the arrested progression of neurodegenerative disease in the three treated patients demonstrate that the transplanted cells, or their progeny, can seed the nervous system and deliver therapeutic levels of active enzyme.
Partial phenotypic correction and immune tolerance induction to enzyme replacement therapy after hematopoietic stem cell gene transfer of α‐glucosidase in Pompe disease
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This work investigated for the first time the use of hematopoietic stem cell (HSC) gene therapy in a murine model of GSDII and its results remain heterogeneous in skeletal muscle, especially in cross reactive immunological material (CRIM)‐negative patients.
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