RESET Project

REStore normal hematopoiesis – Stem cells in congenital hematopoietic disorders: from pathogenesis to innovative therapies.

More INFORMATION

The RESET project (REStore normal hematopoiesis – Stem cells in congenital hematopoietic disorders: from pathogenesis to innovative therapies)

It involves the broad diagnosis of congenital hematopoietic disorders (see -> IBMFS) and aims to introduce effective therapy for bone marrow failure syndromes.

Currently available treatment methods for patients with IBMFS are suboptimal. There is a need to develop new, safer therapies based on genome correction using autologous cells.

The project involves the creation of a repository of cryopreserved cells from patients with congenital bone marrow deficiencies, which will enable subsequent advanced multimodal analyses based on RNA and DNA sequencing at the single-cell level.

The collection of high-quality patient material will enable the implementation of innovative research strategies, such as profiling somatic mitochondrial DNA mutations in single cells, as specific markers for tracking clonal progression. Furthermore, serum banking is planned for the study subgroup of patients, in order to search for biomarkers of clonal progression or somatic reversion (e.g., proteomic studies, extracellular nucleic acid studies).

The project’s long-term goal is to advance the use of a therapy based on genetic engineering of hematopoietic stem cells to the first-in-human clinical trial phase. This innovative treatment option for IBMFs will extend beyond the scope of the current RESET project in the future.

“RESET Project: Stem cells in congenital hematopoietic disorders – from advanced diagnostics to future innovative therapies” under the National Plan for Reconstruction and Enhancement of Immunity, Component D Efficiency, accessibility and quality of the health care system, Investment D3.1.1 Comprehensive development of research in the field of medical and health sciences, contract number 2024/ABM/03/KPO/KPOD.07.07-IW.07-0153/24-00

STAGE 1

Recruitment of patients with suspected congenital bone marrow failure. Collection of material for testing (peripheral blood, bone marrow).

STAGE 2

Molecular analysis of patient samples. Identification of the genetic basis within known IBMF-associated genes using next-generation sequencing.

STAGE 3

If no pathogenic variants are found in step 2, further genetic analysis based on SNP microarrays, whole exome sequencing (WES), and/or optical genome mapping (OGM) is performed. Identification of the putative genetic cause associated with the hematopoietic defect.

STAGE 4

Establishing a repository of cryopreserved cells from IBMF patients. Establishing a biobank for further research.

STAGE 5

Testing of a genome editing system and viral transduction as a potential therapeutic option in IBMFs.

Project duration:
March 2025 – March 2026