Limiting intestinal iron absorption rescues glial defects and extends lifespan in a Drosophila model of Friedreich ataxia

Limiting intestinal iron absorption rescues glial defects and extends lifespan in a Drosophila model of Friedreich ataxia Ema TURKI, Estelle JULLIAN, Pierre DELAMOTTE, Anne FILIPE, Laura TIXIER CARDOSO, Sandrine MIDDENDORP, Elodie MARTIN, Veronique Monnier bioRxiv 2026.06.04.730074; doi:10.64898/2026.06.04.730074 

 Reducing intestinal iron uptake, either through treatment with bathophenanthroline disulfonic acid (BPS), an extracellular iron chelator, or by gut-specific silencing of the iron transporter Malvolio, nearly doubled fly survival. BPS treatment also improved sensitivity to dietary iron, enhanced locomotor performance, fully restored normal brain size, and prevented glial alterations. Altogether, our findings identify glial cells as early and preferential targets of frataxin deficiency in an iron-dependent manner and support the in vivo relevance of intestinal iron uptake as a potential modulator of disease severity in FRDA.

Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia

Chandra S, Kwak C, Du Z ... Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia, Cell Chemical Biology, 2026; 0.  DOI: 10.1016/j.chembiol.2026.05.004

MR3 treatment modulates molecular signatures in a cell-type-dependent manner, altering pathways related to cardiac contractility in cardiomyocytes and synaptic function in sensory neurons. Mechanistically, MR3 reduces mitochondrial reactive oxygen species and restores membrane potential in FA sensory neurons via potential allosteric reshaping of Miro1 protein. We expand the chemical diversity of this scaffold by conducting ligand-based virtual screening of over 3 billion compounds and identifying previously uncharacterized Miro1 ligands with improved docking and neuroprotective capacity.