2020
DOI: 10.1182/blood-2020-137246
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Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: A Global Phase 1 Study for Adult and Pediatric Patients

Abstract: Introduction: Pyruvate Kinase Deficiency (PKD) is a rare inherited hemolytic anemia that is caused by mutations in the PKLR gene leading to decreased red cell pyruvate kinase (RPK) activity and impaired erythrocyte metabolism. The disorder is characterized by anemia, reticulocytosis, splenomegaly and iron overload, and may be life-threatening in severely affected individuals. PKD represents a significant unmet medical need as current therapies are palliative and limited to chronic blood transfusions, iron chel… Show more

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Cited by 10 publications
(12 citation statements)
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“…11 In fact, an international multicentric clinical trial for the treatment of PKD patients is currently on-going (NCT04105166), and has already shown first evidence of therapeutic efficacy. 19 Despite this promising therapy for PKD patients, the emergence of programmable nucleases has revolutionized the gene therapy field, making specific driven integration gene therapy an applicable clinical option. 34 The feasibility of knocking in a cDNA immediately after the start codon of the gene has been recently demonstrated.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…11 In fact, an international multicentric clinical trial for the treatment of PKD patients is currently on-going (NCT04105166), and has already shown first evidence of therapeutic efficacy. 19 Despite this promising therapy for PKD patients, the emergence of programmable nucleases has revolutionized the gene therapy field, making specific driven integration gene therapy an applicable clinical option. 34 The feasibility of knocking in a cDNA immediately after the start codon of the gene has been recently demonstrated.…”
Section: Discussionmentioning
confidence: 99%
“…18 This lentiviral-mediated gene therapy approach would offer a durable and curative clinical benefit with a single treatment, as shown by the preliminary results obtained in the first two patients already infused with transduced autologous hematopoietic stem cells (HSCs) (NCT04105166). 19 Despite the promising results of conventional gene therapy, the ideal gene therapy approach should lead to the specific correction of the mutated gene, maintaining the endogenous regulation and eliminating the integration of exogenous DNA material elsewhere. Gene editing can be used as a therapeutic approach to conduct precise homology directed repair (HDR).…”
Section: Introductionmentioning
confidence: 99%
“…In fact, a first-in-human gene therapy clinical trial for the treatment of PKD (ClinicalTrials.gov: NCT04105166) is currently active, and the initial patients have been treated as of mid-2020; preliminary clinical data were recently updated, and the efficacy and safety profile have, to date, been encouraging and consistent with our preclinical results. 22…”
Section: Discussionmentioning
confidence: 99%
“…Additionally, as initially reported by García-Gómez et al (19) , the correction of the PKLR gene defect by means of lentiviral-mediated gene therapy is feasible and restores RPK functionality. In fact, an international multicentric clinical trial for the treatment of PKD patients is currently on-going (NCT04105166), and has already shown first evidences of therapeutic efficacy (20) . Despite this promising therapy for PKD patients, the emergence of programmable nucleases has revolutionized the gene therapy field, making specific driven integration gene therapy an applicable clinical option (36) .…”
Section: Discussionmentioning
confidence: 99%
“…We have recently developed a lentiviral vector to genetically correct PKD (19) , which has been granted orphan drug designation by the European and the American office regulators (EU/3/14/1330; FDA #DRU-2016-5168). This lentiviral-mediated gene therapy approach would offer a durable and curative clinical benefit with a single treatment, as shown by the preliminary results obtained in the first patient already infused with transduced autologous HSCs (NCT04105166) (20) .…”
Section: Introductionmentioning
confidence: 99%