Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Preclinical quality, safety and efficacy of a human embryonic stem cell-derived product for treatment of people with moderate Parkinson’s Disease (STEM-PD) III

ABSTRACT: Cell replacement therapies for Parkinson’s Disease (PD) based on transplantation of dopaminergic neurons generated from pluripotent stem cell sources are now entering clinical trials. Here, we present the quality, safety and efficacy data supporting a first-in-human clinical trial in PD using an embryonic stem cell product STEM-PD, as well as the design of the trial itself. The cryopreserved STEM-PD product was manufactured under Good Manufacturing Practice (GMP) and fully quality-tested in vitro for regulatory compliance. The product was further tested in an extensive 39-week Good Laboratory Practice (GLP) safety study in immunodeficient rats for toxicity, tumourigenicity and biodistribution, as well as in a 24-week non-GLP efficacy study. These studies showed that the transplanted STEM-PD cells could induce full functional recovery in a pre-clinical rat model of PD, and that the treatment did not give rise to any adverse effects. This cell batch will be used for all participants in the STEM-PD Phase I/IIa clinical trial, where the first of 8 patients with moderate PD have now been transplanted. Furthermore, we observed highly comparable in vivo efficacy results between two different GMP batches of STEM-PD cells, verifying that this product has the potential to be serially manufactured for widespread clinical use.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229768 | GEO | 2023/09/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Preclinical quality, safety and efficacy of a human embryonic stem cell-derived product for treatment of people with moderate Parkinson’s Disease (STEM-PD) II

Project description:Cell replacement therapies for Parkinson’s Disease (PD) based on transplantation of dopaminergic neurons generated from pluripotent stem cell sources are now entering clinical trials. Here, we present the quality, safety and efficacy data supporting a first-in-human clinical trial in PD using an embryonic stem cell product STEM-PD, as well as the design of the trial itself. The cryopreserved STEM-PD product was manufactured under Good Manufacturing Practice (GMP) and fully quality-tested in vitro for regulatory compliance. The product was further tested in an extensive 39-week Good Laboratory Practice (GLP) safety study in immunodeficient rats for toxicity, tumourigenicity and biodistribution, as well as in a 24-week non-GLP efficacy study. These studies showed that the transplanted STEM-PD cells could induce full functional recovery in a pre-clinical rat model of PD, and that the treatment did not give rise to any adverse effects. This cell batch will be used for all participants in the STEM-PD Phase I/IIa clinical trial, where the first of 8 patients with moderate PD have now been transplanted. Furthermore, we observed highly comparable in vivo efficacy results between two different GMP batches of STEM-PD cells, verifying that this product has the potential to be serially manufactured for widespread clinical use.

2023-09-25 | GSE229767 | GEO

Preclinical quality, safety and efficacy of a human embryonic stem cell-derived product for treatment of people with moderate Parkinson’s Disease (STEM-PD) I

2023-09-25 | GSE229766 | GEO

Assessment of gene expression changes in ex vivo-expanded human skin-derived ABCB5-selected mesenchymal stem cells during passaging

Project description:To evaluate the potential impact of multiple passaging on the homogeneity of ex vivo-expanded, GMP-manufactured human skin-derived ABCB5+ mesenchymal stem cells, comparative gene expression profile analysis on cells from various passages was employed.

2020-02-21 | GSE145589 | GEO

Transcriptome of human peripheral blood regulatory T cells with distinct ex vivo expansion profile

Project description:The UCSF Treg cell therapy program manufactured over 60 human regulatory T cell (Treg) products under the GMP condition in support of 9 clinical trials between 2011 and 2021. These products were manufactured using two alternative protocols of either two rounds of polyclonal stimulations (PolyTregs) or first allogeneic B cell stimulation followed by polyclonal stimulation (arTregs). A high degree of individual variability in Treg expansion with both protocols was observed. RNA-seq analysis was performed on freshly isolated peripheral blood Tregs to identify transcriptome profile associated with Treg expansions.

2024-04-17 | GSE208111 | GEO

Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease

Project description:The pre-clinical efficacy and safety data support the initiation of a phase I/II clinical trial for β-globin gene correction in patient-derived hematopoietic stem cells for the treatment of sickle cell disease.

2021-05-16 | GSE163912 | GEO

Reversal of post-hepatectomy liver failure using a bioartifical liver supporting system implanted with clinical-grade human induced hepatocytes

Project description:Here, we developed a clinical-grade bioartificial liver (BAL) device by implanting with directly reprogrammed human hepatocytes (hiHep) manufactured and cryopreserved under current good manufacturing practice (cGMP) conditions. Notably, in a porcine PHLF model induced by 85% hepatectomy, hiHep-BAL treatment showed a remarkable survival benefit, as well as improvements of liver metabolic gene expression, ammonia detoxification, and liver regeneration. Furthermore, an investigator-initiated study in seven patients with extended liver resection (NCT05035108) demonstrated that hiHep-BAL treatment was well tolerated without complications and associated with ameliorative liver function and remarkable liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant the further efficacy testing of hiHep-BAL for PHLF followed by the future broadening the patients eligible for liver resection in clinics.

2023-04-05 | GSE200124 | GEO

Evaluating the utility of proteomics for the identification of circulating pharmacodynamic biomarkers of IFNβ-1 biologics

Project description:In this study, we evaluated the utility of proteomics to identify plasma proteins in healthy participants from a phase I clinical trial with IFNβ-1a and pegIFNβ-1a biologics to identify potential pharmacodynamic (PD) biomarkers. Using a linear mixed-effects model with repeated measurement for product-time interaction, we found that 248 and 528 analytes detected by the SOMAscan® assay were differentially expressed (p-value < 6.86E-06) between therapeutic doses of IFNβ-1a or pegIFNβ-1a, and placebo, respectively. We further prioritized signals based on peak change, area under the effect curve over the study duration, and overlap in signals from the two products. Analysis of prioritized datasets indicated activation of IFNB1 signaling and an IFNB signaling node with IL-6 as upstream regulators of the plasma protein patterns from both products. Increased TNF, IL-1B, IFNG, and IFNA signaling also occurred early in response to each product suggesting a direct link between each product and these upstream regulators. In summary, we identified longitudinal global PD changes in a large array of new and previously reported circulating proteins in healthy participants treated with IFNβ-1a and pegIFNβ-1a that may help identify novel single proteomic PD biomarkers and/or composite PD biomarker signatures as well as provide insight into the mechanism of action of these products. Independent replication is needed to confirm present proteomic results and to support further investigation of the identified candidate PD biomarkers for biosimilar product development.

2023-10-31 | GSE207945 | GEO

Proteome characterization of the neoadjuvant clinical trial PROMIX

Project description:Proteome characterization of the neoadjuvant clinical trial PROMIX. https://www.clinicaltrials.gov/ct2/show/NCT00957125 Patients received six rounds of chemotherapy with epirubicin and docetaxel, and if PR or PD after the second course, bevacizumab.

2024-03-19 | PXD039529 | JPOST Repository

Adaptive single-KIR+NKG2C+ NK cells expanded from superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia

Project description:Describe a novel GMP-compliant protocol to expand clinically relevant numbers of adaptive NK cells from third-party ‘superdonors’. These NK cells provide strong reactivity in a mouse model of AML as well as against primary AML blasts ex vivo. How this study might affect research, practice or policy: These pre-clinical data demonstrate the feasibility of an NK cell-based cell therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing-self recognition.

2022-09-20 | E-MTAB-12228 | biostudies-arrayexpress

Glucagon-like Peptide-1 (GLP-1) Rescue Diabetic Cardiac Dysfuntions in Human iPSC-Derived Cardiomyocytes

Project description:We investigate the effects of GLP-1 on diabetic cardiomyocytes (DCMs) model established by human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs). Two subtypes of GLP-1, GLP-17-36 and GLP-19-36, were evaluated for their efficacy on hypertrophic phenotype, impaired calcium homeostasis and electrophysiological properties. RNA-seq was performed to reveal the underlying molecular mechanism of GLP-1. Our results demonstrated that GLP-17-36 and GLP-19-36 were able to ameliorate high glucose-induced hypertrophy phenotype and cardiac dysfunctions in DCM model based on iPSC-CMs. Our study provides a novel platform to unveil the cellular mechanisms of diabetic cardiomyopathy, which sheds light on discovering better targets for novel therapeutic interventions.

2022-07-01 | GSE197850 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data