Evaluating the Effects of Statins and Bisphosphonates on the Radiosensitivity of Friedreich’s Ataxia

Abstract

Introduction: Friedreich’s Ataxia (FRDA) is a rare neurodegenerative disorder caused by frataxin deficiency, leading to mitochondrial dysfunction, oxidative stress, and increased cellular susceptibility to DNA damage. Recent studies have suggested that statins and bisphosphonates may modulate oxidative stress and influence DNA repair pathways, thereby potentially altering radiosensitivity.

Aim: This study aimed to evaluate the effects of statins and bisphosphonates on the radiosensitivity of FRDA fibroblast cell lines.

Materials and methods: Immunofluorescence was performed on two FRDA fibroblast cell lines and one normal fibroblast cell line to assess DNA damage response and cell survival following ionizing radiation exposure, using two biomarkers, pATM and γH2AX. Clonogenic assay was performed to assess cell survival.

Results: In normal fibroblasts, Zo, Pra, and ZoPra pretreatments did not significantly modify pATM or γ-H2AX foci induction after irradiation. In FRDA fibroblasts, ZoPra increased pATM and γ-H2AX foci at 10 min post-IR, reduced residual γ-H2AX foci at 24 h.

Conclusion: These findings indicate that ZoPra enhances DNA double-strand break repair in FRDA fibroblasts, reducing radiosensitivity and genomic instability. Our results suggest that ZoPra can be an effective radioprotective drug in FRDA patients.