Redox homeostasis and Inflammation in fibroblasts of patients with Friedreich Ataxia: a possible cross talk

Andrea Quatrana, Sara Petrillo Sara Petrillo, Caterina Torda Caterina Torda, Eleonora De Santis, Enrico Bertini Enrico Bertini, Fiorella Piemonte. Front. Mol. Neurosci., Sec. Molecular Signalling and Pathways, Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1571402.

We found a significant activation of the TLR4/NF-kB/IL-1β axis in patients, associated to a consistent increase of the redox enzymes thioredoxin 1 (TRX1) and glutaredoxin 1 (GLRX1), which are essential to activate NF-kB under oxidative stress conditions. Furthermore, we investigated the role of 4-HNE, a by-product of lipid peroxidation, as a potential mediator between ferroptosis and inflammation in FRDA.

Systemic AAV Gene Therapy with Next Generation Engineered Capsids for Treatment of CNS and Cardiac Symptoms in Friedreich’s Ataxia

MDA Conference 2025. Ryan Kast, PhD, Capsida Biotherapeutics, Celeste Stephany, PhD, Capsida Biotherapeutics, Miguel Chuapoco, PhD, Capsida Biotherapeutics, Xiaojing Shi, PhD, Capsida Biotherapeutics, Assaf Beck, PhD, Capsida Biotherapeutics, Austin Kidder, Capsida Biotherapeutics, Yixi Wang, Capsida Biotherapeutics, Kevin Lam, Capsida Biotherapeutics, Nicholas Flytzanis, PhD, Capsida Biotherapeutics, Nick Goeden, PhD, Capsida Biotherapeutics. The engineered capsid delivering human FXN transduced more than 80% of cerebellar Purkinje cells, dentate nucleus neurons, motor neurons in the cortex and spinal cord, and nearly 30% of cardiac tissue area. FXN protein levels in treated NHPs were 8.2x higher than endogenous levels in the motor cortex and 1.7x in the heart as measured by ELISA. Moreover, substantial FXN RNA expression was detected in the retina (~1E6 copies/ug RNA) suggesting potential benefit for sensory vision loss experienced by FA patients. Significant de-targeting of the liver and other non-target tissues contributed to the favorable safety profile characterized by no adverse immunogenicity, clinical pathology, and histopathology findings.