Scientists at IRB Barcelona, based at the Barcelona Science Park, reveal defects in amino acid transport that reduce erythropoietin production and compromise red blood cell formation. The research, published in the journal Molecular Medicine and led by Dr. Manuel Palacín and Dr. Susanna Bodoy, demonstrates that deficiency of the SLC7A7 protein causes a reduction in erythropoietin and, consequently, a defect in red blood cell production. The iron metabolism expert groups of Dr. Günter Weiss (Medical University of Innsbruck) and Dr. Mayka Sánchez (International University of Catalonia) have collaborated in the study.

This finding allows a deeper understanding of the molecular bases of anaemia associated with Lysinuric Protein Intolerance (LPI). LPI is a rare disease caused by mutations in the Slc7a7 gene that lead to defective transport of neutral and basic amino acids. Despite being a rare disease, LPI causes complications in multiple organs and systems. The main approach to treatment is through a low-protein diet combined with citrulline. However, patients often continue to present haematological and immunological alterations. “Our results indicate that depletion of erythropoietin in the kidney is key to understanding the problems in red blood formation,” explains Dr. Palacín, head of the Amino Acid Transporters and Disease lab at IRB Barcelona and professor of the Biochemistry and Molecular Biology Department of the Faculty of Biology at the University of Barcelona. “This paves the way for new therapeutic approaches specifically aimed at correcting the production of erythropoietin,” he adds.

To undertake the study, the team used mice with complete deletion of the Slc7a7 gene, as well as models in which the deletion was restricted exclusively to different types of blood cells. The analyses showed that the lack of SLC7A7 at the systemic level caused a disruption of erythropoiesis and an increase in iron levels.

However, the limited deficiency in different types of blood cells did not cause these issues, thereby pointing to the kidney as the origin. Furthermore, bone marrow transplants did not reverse the haematological defects, thus supporting the notion that the problem is extrinsic to hematopoietic cells.

The findings highlight the need to explore new therapeutic approaches that, beyond diet and citrulline supplementation, focus on restoring erythropoietin production to prevent the haematological complications of LPI.

» Article of reference: Defective Slc7a7 transport reduces erythropoietin compromising erythropoiesis. Judith Giroud-Gerbetant, Fernando Sotillo, Gonzalo Hernández, Irene Ruano, David Sebastián, Joana Fort, Mayka Sánchez, Günter Weiss, Neus Prats, Antonio Zorzano, Manuel Palacín, Susanna Bodoy. Molecular Medicine (2025) doi: 10.1186/s10020-025-01100-0

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