Ferroptosis—disease perils and therapeutic promise

Ashley R. Brown et al. ,Ferroptosis—disease perils and therapeutic promise.Science386,848-849(2024).DOI:10.1126/science.adn703 

Identifying new strategies to inhibit ferroptosis offers therapeutic promise in contexts where ferroptotic cell death contributes to disease progression. By contrast, selective induction of ferroptosis is a promising approach in cancer therapeutics. Continuing discoveries about the mechanisms governing ferroptosis are likely to improve our understanding of disease biology and provide ideas that may assist in the diagnosis and treatment of diverse human maladies.

Therapeutic Activity of a Haematopoietic Stem Cell-Delivered Tissue-Penetrating Peptide in Friedreich's Ataxia Models

Pido, Jeffrey and Shaban, Enas and Moula, Shefta and Chritchely, Bethan and Whittaker, Thomas and Svensson, Stina and Anjomani Virmouni, Sara and Kalef-Ezra, Ester and Carr, Lucinda and Hassell, Jane and Thrasher, Adrian J. and Kurian, Manju A. and Santilli, Giorgia and Sala, Arturo and Administrator, Sneak Peek, Therapeutic Activity of a Haematopoietic Stem Cell-Delivered Tissue-Penetrating Peptide in Friedreich's Ataxia Models. doi:10.2139/ssrn.5026639 

We developed a replacement strategy for this disease by designing a fusion peptide containing secretion and tissue penetrating sequences at the amino terminus of the frataxin precursor protein. Secretion and penetration of the fusion peptide was validated in experiments that confirmed its ability to localise in the mitochondria and rescue the biochemical defects and apoptotic phenotype of FRDA patient cells, in vitro. Autologous transplantation of the modified HSPCs resulted in stable secretion of the peptide in the blood stream of recipient animals, impacting disease progression by delaying the manifestation of motor-coordination/sensory symptoms, paralleled by improved biochemical and anatomical parameters.