Cells heal themselves: gene-edited hematopoietic stem cells restore frataxin deficiency in multiple organs.
Abstract
Friedreich's ataxia (FRDA) is a triplet repeat expansion disorder with multisystem, progressive symptoms caused by reduced frataxin protein levels and compromised mitochondrial function. Restoration of frataxin protein is a focus of clinical trials involving adeno-associated viral vectors, but substantial barriers exist because of the immune response they elicit. In this issue of the JCI, Sivakumar et al. harnessed CRISPR/Cas9 editing of endogenous hematopoietic stem and progenitor cells (HSPCs) to excise the frataxin gene (FXN) repeat expansion ex vivo, followed by autologous transplantation. A single, systemic infusion of corrected HSPCs resulted in long-term engraftment and sustained multiorgan benefit in a humanized mouse model of FRDA. This improvement in brain, cardiac, and pancreatic symptoms, mediated by myeloid progeny of the engrafted stem cells, provides strong support for the potential effectiveness of this approach in humans and bypasses the need to correct the FXN deficiency in the affected tissue and cells directly.
Related
- Edited HSPCs rescue frataxin deficiency and inflammation-driven multisystemic pathology in Friedreich's ataxia mice.
- Hematopoietic cell transplantation using treosulfan-based conditioning for IL-10 receptor deficiency
- BCL10 deficiency: Long-term immune reconstitution following hematopoietic stem cell transplantation.
- Case Report: Fulminant aggressive NK-cell leukemia with hemophagocytic lymphohistiocytosis and multiple organ dysfunction successfully bridged to allogeneic hematopoietic stem cell transplantation
- Crystal Structure of Bacillus subtilis Cysteine Desulfurase SufS and Its Dynamic Interaction with Frataxin and Scaffold Protein SufU.
BibTeX
@article{osborne2026cells,
title = {{Cells heal themselves: gene-edited hematopoietic stem cells restore frataxin deficiency in multiple organs.}},
author = {Lucy R Osborne},
journal = {The Journal of clinical investigation},
year = {2026},
month = oct,
doi = {10.1172/jci211630},
url = {https://europepmc.org/article/MED/42878081},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cells heal themselves: gene-edited hematopoietic stem cells restore frataxin deficiency in multiple organs.
AU - Lucy R Osborne
PY - 2026
DA - 2026/10/15
JO - The Journal of clinical investigation
DO - 10.1172/jci211630
UR - https://europepmc.org/article/MED/42878081
AB - Friedreich's ataxia (FRDA) is a triplet repeat expansion disorder with multisystem, progressive symptoms caused by reduced frataxin protein levels and compromised mitochondrial function. Restoration of frataxin protein is a focus of clinical trials involving adeno-associated viral vectors, but substantial barriers exist because of the immune response they elicit. In this issue of the JCI, Sivakumar et al. harnessed CRISPR/Cas9 editing of endogenous hematopoietic stem and progenitor cells (HSPCs) to excise the frataxin gene (FXN) repeat expansion ex vivo, followed by autologous transplantation. A single, systemic infusion of corrected HSPCs resulted in long-term engraftment and sustained multiorgan benefit in a humanized mouse model of FRDA. This improvement in brain, cardiac, and pancreatic symptoms, mediated by myeloid progeny of the engrafted stem cells, provides strong support for the potential effectiveness of this approach in humans and bypasses the need to correct the FXN deficiency in the affected tissue and cells directly.
SN - 0021-9738
SN - 1558-8238
ER -