A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers

Szczepiórkowski, Zbigniew M.; Siegel, Alan; Ferrari, Antonio; Mambrini, Giovanni; Anand, Ravi; Hartman, Richard D.; Benatti, Luca; Dumont, Larry J.

doi:10.1016/j.tmrv.2017.09.001

Cited by 28 publications

(19 citation statements)

References 34 publications

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“…As a result of the deprioritization, the current Phase 1b clinical trial in PKU will be discontinued." Table 2 Clinical trials considered in this article related to the use of red blood cells loaded with therapeutic agents FDA criteria for the approval of blood transfusion products [14]. Erytech, based on asparaginase activity [30], has shown that the entrapped asparaginase is detectable in circulation for about 1 month.…”

Section: Discussionmentioning

confidence: 99%

“…The idea of using a non-diffusible prodrug of dexamethasone using autologous erythrocytes was also very beneficial in terms of pharmacokinetics. In fact, Dexa 21-P is slowly converted to the diffusible dexamethasone by RBC resident enzymes and detected in circulation for > 1 month in human volunteers receiving a single infusion of Dexa 21-P-loaded RBCs [14]. In the same study sponsored by EryDel SpA, it was also shown that the processed RBCs have normal in vivo survival and are fully compliant with the rules for FDA-defined transfusion products.…”

Section: Red Blood Cells (Rbcs) For the Delivery Of Dexamethasonementioning

confidence: 99%

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Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

et al. 2020

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Engineered red blood cells (RBCs) appear to be a promising method for therapeutic drug and protein delivery. With a number of agents in clinical trials (e.g., dexamethasone 21-phosphate in ataxia telangiectasia, asparaginase in pancreatic cancer/acute lymphoblastic leukemia, thymidine phosphorylase in mitochondrial neurogastrointestinal encephalomyopathy, RTX-134 in phenylketonuria, etc.), this leading article summarizes the ongoing efforts in developing these agents, focuses on the clinical progress, and provides a brief background into engineered RBCs and the different ways in which they can be exploited for therapeutic/diagnostic purposes. References to available data on safety, efficacy, and tolerability are reported. Due to the continuous progress in this field, the information is updated as of January 2020 from databases, websites, and press releases of the involved companies and information that is in the public domain.

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Section: Discussionmentioning

confidence: 99%

Section: Red Blood Cells (Rbcs) For the Delivery Of Dexamethasonementioning

confidence: 99%

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

et al. 2020

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“…Due to better care, life expectancy of A-T patients has emerged over the last decades (45). Especially in the light of new treatment options such as bone marrow transplantation (46)(47)(48), dexamethasone treatment (49)(50)(51), and gene therapy (52-54) disease facets with manifestation in the later disease course should be screened and treated. According to our data, diabetes screening is indicated starting for the age of 12 years.…”

Section: Discussionmentioning

confidence: 99%

Diabetes in Patients With Ataxia Telangiectasia: A National Cohort Study

et al. 2020

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Background: Ataxia telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition and altered body composition. In addition, evidence is rising for endocrine dysfunction. Objectives: To determine the evolution of diabetes and its prevalence in a larger AT cohort. Methods: A retrospective analysis of the patient charts of 39 subjects from the Frankfurt AT cohort was performed between August 2002 and 2018 concerning HbA1c and oral glucose tolerance (OGTT). The median follow-up period was 4 years (1-16 years). In addition, in 31 AT patients aged 1 to 38 years HbA1c and fasting glucose were studied prospectively from 2018 to 2019. Results: In the retrospective analysis, we could demonstrate a longitudinal increase of HbA1c. The prospective analysis showed a significant increase of HbA1c and fasting glucose with age (r = 0.79, p ≤ 0.0001). OGTT has a good sensitivity for insulin resistance screening, whereas HbA1c can be used to evaluate individual courses and therapy response. Seven out of 39 (17.9%) patients suffered from diabetes. Metformin did not always lead to sufficient diabetes control; one patient was treated successfully with repaglinide. Conclusion: Diabetes is a common finding in older AT patients and often starts in puberty. Our data clearly demonstrate the need for an annual diabetes screening in patients > 12 years.

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“…Due to better care, life expectancy of A-T patients has emerged over the last decades (44). Especially in the light of new treatment options such as bone marrow transplantation (45)(46)(47), dexamethasone treatment (48)(49)(50) and gene therapy (51)(52)(53) disease facets with manifestation in the later disease course should be screened and treated. According to our data, diabetes screening is indicated starting for the age of 12 years.…”

Section: Patientmentioning

confidence: 99%

Diabetes in Patients with Ataxia telangiectasia: A National Cohort Study

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Kieslich

et al. 2020

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Background: Ataxia telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition and altered body composition. In addition, evidence is rising for endocrine dysfunction. Objectives: To determine the evolution of diabetes and its prevalence in a larger A-T cohort. Methods: A retrospective analysis of the patient charts of 39 subjects from the Frankfurt A-T cohort was performed between August 2002 and 2018 concerning HbA1c and oral glucose tolerance (OGTT). The median follow-up period was 4 years (1-16 years). In addition, in 31 A-T patients aged 1 to 38 years HbA1c and fasting glucose were studied prospectively from 2018-2019. Results: In the retrospective analysis, we could demonstrate a longitudinal increase of HbA1c. The prospective analysis showed a significant increase of HbA1c and fasting glucose with age (r = 0.79, p <0.0001). OGTT has a good sensitivity for IR screening, whereas HbA1c can be used to evaluate individual courses and therapy response. Seven out of 39 (17.9%) patients suffered from diabetes. Metformin did not always lead to sufficient diabetes control; one patient was treated successfully with repaglinide. Conclusion: Diabetes is a common finding in older A-T patients and often starts in puberty. Our data clearly demonstrate the need for an annual diabetes screening in patients > 12 years.

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A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers

Cited by 28 publications

References 34 publications

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

Ongoing Developments and Clinical Progress in Drug-Loaded Red Blood Cell Technologies

Diabetes in Patients With Ataxia Telangiectasia: A National Cohort Study

Diabetes in Patients with Ataxia telangiectasia: A National Cohort Study

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