The Neuroinflammatory Decoupling Index — A Dynamic Biomarker of ALS Progression

Abstract Currently, there is no reliable biomarker that accurately reflects the progression rate of Amyotrophic Lateral Sclerosis (ALS). Existing measures either depend on subjective clinical assessment or detect neuronal damage without distinguishing between primary disease effects and secondary inflammatory acceleration. This work proposes a novel concept: the Neuroinflammatory Decoupling Index (NDI) — a ratio between the rate of change of inflammatory markers and the rate of change of neuronal damage markers. Preliminary evidence from three independent peer-reviewed studies supports this hypothesis. However, the original InnoCentive/Prize4Life challenge portal where this concept was initially intended for submission is currently inaccessible due to unauthorized link redirection; therefore, this work is being made available directly through Zenodo to ensure open and permanent access to the scientific community. The NDI may serve as a simple, dynamic, and easily measurable biomarker that could improve clinical trial sensitivity and help distinguish effective therapies from treatments that only target one aspect of the disease process.