NPJ systems biology and applicationsNov 25, 2025

Computer model of ATM cell repair signaling to predict drugs for ataxia-telangiectasia

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A computational model suggested that combining autophagy activation with epigenetic modulation could partially restore ATM-deficient cell homeostasis.

Evidence

Computational systems biology work used ordinary differential equation modeling in COPASI to simulate physiological, ATM-deficient, and drug-treated signaling states for spermidine, omaveloxolone, and HDAC4 inhibition.

Caveat

The therapeutic claims are model-based predictions supported by sensitivity, stability, and enrichment analyses, not experimental or clinical treatment outcomes.

Simplified

(A-T) is a rare genetic disorder caused by ATM mutations, leading to impaired DNA repair, oxidative stress, and neurodegeneration. We developed a computational model of ATM-mediated signaling using ordinary differential equations in COPASI, capturing key processes including DNA damage sensing, cell cycle regulation, autophagy, and oxidative stress response. The model simulates physiological, ATM-deficient, and drug-treated conditions to explore repurposing strategies. We evaluated the effects of spermidine, omaveloxolone, and HDAC4 inhibition, revealing mechanisms by which these compounds modulate dysfunctional signaling. Sensitivity and stability analyses confirmed the model's robustness, while enrichment analysis validated involvement of key pathways. Our results highlight the synergistic potential of combining autophagy activation and epigenetic modulation to partially restore homeostasis in ATM-deficient cells. This work introduces a generalizable modeling framework for simulating disease-specific signaling dysfunction and identifying therapeutic interventions, illustrating the value of computational systems biology in rare disease .

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PubMed

Computer model of ATM cell repair signaling to predict drugs for ataxia-telangiectasia

Abstract

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