2021
DOI: 10.1038/s41467-021-21371-5
|View full text |Cite
|
Sign up to set email alerts
|

Lentivirus-mediated gene therapy for Fabry disease

Abstract: Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34+-selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloabla… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2
1

Citation Types

1
55
0
2

Year Published

2021
2021
2024
2024

Publication Types

Select...
4
2
1
1

Relationship

0
8

Authors

Journals

citations
Cited by 82 publications
(58 citation statements)
references
References 36 publications
1
55
0
2
Order By: Relevance
“…In the first gene therapy pilot project for FD, Khan et al demonstrated efficient LV-mediated gene transfer into enriched Fabry patient CD34+ cells. They reported increased circulating and intracellular GLA activity, without serious safety concerns [74]. All Fabry patients (n = 5) in this pilot trial were responsive to the LV-mediated gene therapy at some level; all patients produced GLA to near normal level within one week, plasma and leukocytes demonstrates GLA activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) have been demonstrated.…”
Section: Future Treatment Options/investigational Therapiesmentioning
confidence: 84%
See 1 more Smart Citation
“…In the first gene therapy pilot project for FD, Khan et al demonstrated efficient LV-mediated gene transfer into enriched Fabry patient CD34+ cells. They reported increased circulating and intracellular GLA activity, without serious safety concerns [74]. All Fabry patients (n = 5) in this pilot trial were responsive to the LV-mediated gene therapy at some level; all patients produced GLA to near normal level within one week, plasma and leukocytes demonstrates GLA activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) have been demonstrated.…”
Section: Future Treatment Options/investigational Therapiesmentioning
confidence: 84%
“…All Fabry patients (n = 5) in this pilot trial were responsive to the LV-mediated gene therapy at some level; all patients produced GLA to near normal level within one week, plasma and leukocytes demonstrates GLA activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) have been demonstrated. Three patients have elected to discontinue enzyme replacement [74]. Persistent elevation of GLA activity in patients has demonstrated early safety of the protocol for this ex vivo approach, as shown also by a press release from AVROBIO [75].…”
Section: Future Treatment Options/investigational Therapiesmentioning
confidence: 98%
“…Agalsidase α is generated from a continuous human cell line with the activation of the GLA gene, while agalsidase β is generated from a Chinese hamster ovary mammalian cell expression system transduced with the human GLA sequence. Enzyme replacement therapy has been shown to effectively reduce glycolipid substrates including Gb 3 in the urine, plasma, and tissues of patients with FD [ 51 ]. With respect to FD-related cardiac injury, ERT has been shown to effectively reduce Gb 3 inclusions in endothelial cells, with less clear evidence regarding Gb 3 clearance from cardiomyocytes [ 52 ].…”
Section: Treatments In Fabry Diseasementioning
confidence: 99%
“…Functional α-Gal A enzymes are then subsequently secreted into the circulation, which can be taken up by affected cells [ 65 ]. Recently, the first gene therapy trial for FD was conducted, where classical FD patients were infused with lentivirus-transduced hematopoietic stem cells engineered to express α-Gal A [ 51 ]. All patients produced α-Gal A to near normal levels within one week of therapy with observations of reduced plasma and urine Gb 3 [ 51 ].…”
Section: Future Directions In the Management Of Fabry Diseasementioning
confidence: 99%
“…Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) is a well-established paradigm for treating monogenic diseases, with more than 300 patients currently dosed [1][2][3][4] . Clinical applications of HSPC-GT include treatments of inherited immune deficiencies (e.g., SCID-X1, ADA-SCID, Wiskott-Aldrich syndrome), blood disorders (e.g., sickle cell disease, transfusion-dependent beta-thalassemia, Xlinked chronic granulomatous disease), and lysosomal storage disorders (e.g., Hurler syndrome, Hunter syndrome, Fabry disease) [5][6][7][8][9][10][11][12][13] . In general, a patient's bone marrow cells are mobilized and collected from the periphery and HSPCs are isolated and transduced ex vivo with a lentiviral vector carrying a therapeutic payload.…”
Section: Introductionmentioning
confidence: 99%