Collection of Samples of Bone Marrow Aspiration From Patients With Myelodysplastic Syndrome
- Conditions
- Myelodysplastic Syndromes
- Interventions
- Procedure: Blood test
- Registration Number
- NCT06144515
- Lead Sponsor
- Minovia Therapeutics Ltd.
- Brief Summary
The study Objective is to collect samples of bone marrow aspirates and peripheral blood of patients with MDS for use in non-clinical research to investigate mitochondrial function sequence and effect of mitochondrial augmentation.
- Detailed Description
Mitochondrial dysfunction is often associated with MDS. Studies have shown mitochondrial DNA (mtDNA) mutations in different MDS subtypes; however, their role in the pathogenesis and disease progression are not yet clear. Point mutations were found in various locations in the mitochondrial genome including tRNAs, rRNAs, and mitochondrial proteins.
Mitochondrial fragmentation in hematopoietic stem and progenitor cells (HSPC) can lead to ineffective hematopoiesis in MDS, suggesting mitochondria as a therapeutic target for treating MDS.
Mitochondria augmentation therapy (MAT) is a novel cell technology where hematopoietic stem and progenitor cells (HSPCs) are augmented ex vivo with mitochondria obtained from donor cells or tissue. MAT is based on the demonstrated ability of isolated mitochondria to enter cells and impact mitochondrial function and metabolic activity in the recipient cells. The transfer of mitochondria from cell to cell has been demonstrated using extracellular vesicles, nanotubes, and micropinocytosis. Mitochondria entering cells provide copies of normal mtDNA, which can be further propagated via replication within the recipient cell and via intercellular transfer.
Research will include in vitro and in vivo studies with the bone marrow sample, including, among other, the following: mitochondrial augmentation of bone marrow aspiration and/or subpopulations of cells (e.g. CD34+) isolated from the bone marrow aspiration; differentiation of augmented and/or non-augmented bone marrow aspiration and/or subpopulations of cells into hematopoietic lineages (e.g. erythroid, megakaryocyte, etc); assays of mitochondrial content and function; assays of hematopoietic lineages; culture of augmented and/or non-augmented bone marrow aspiration and/or subpopulations; cryopreservation of augmented and/or non-augmented bone marrow aspiration and/or subpopulations; sequencing of mitochondrial DNA and nuclear DNA; in vivo studies of engraftment, biodistribution and function of augmented and/or non-augmented bone marrow aspiration and/or subpopulations of cells isolated from the bone marrow aspiration.
Research will include in vitro studies with the peripheral blood sample, including, among other, the following: immunophenotyping of peripheral blood cells and immune-related functional assays; mitochondrial content and function of peripheral blood cells.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Male or female patients of 18 years old and up.
- Suspected or previously diagnosed with Myelodysplastic Syndrome.
- Patient able to understand and provide voluntary written informed consent.
- History of prior allogeneic hematopoietic stem cell transplantation, cell therapy, gene therapy.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Collection of Samples of Bone Marrow Aspiration From Patients With Myelodysplastic Syndrome Blood test -
- Primary Outcome Measures
Name Time Method Investigate mitochondrial content and function in MDS patient-derived cells 1 Year assays of mitochondrial content and function on whole bone marrow and HSPCs assays of hematopoietic lineages;
investigate effect of mitochondrial augmentation on MDS patient-derived cells 1 Year in vivo studies of engraftment, biodistribution and function of augmented and/or non-augmented bone marrow aspiration and/or subpopulations of cells isolated from the bone marrow aspiration., in vitro ability to differentiate to various hematopoeitic lineages, immunophenotyping and single cells studies of cells post-augmentation and post-differentiation
Persistence of exogenous mtDNA after mitochondrial augmentation 1 year Persistence of exogenous mtDNA after in vitro or in vivo culturing
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel