An RNA aptamer-based tool for the detection of pathological protein aggregates in biofluids

Descripción del proyecto

Detección temprana de la esclerosis lateral amiotrófica con aptámeros de ARN

La detección temprana y precisa de la esclerosis lateral amiotrófica (ELA o ALS, por sus siglas en inglés), una enfermedad neurodegenerativa que provoca la pérdida de neuronas y del control muscular, es el primer paso para una intervención terapéutica oportuna. Sin embargo, detectar agregados de TDP-43, que son agregados proteicos anómalos que se acumulan en las neuronas y son característicos de la ELA, constituye uno de los principales retos para un diagnóstico temprano. En este contexto, el proyecto AptALS, financiado por el Consejo Europeo de Investigación, diseñará un kit de diagnóstico basado en aptámeros de ARN que puedan unirse selectivamente a los agregados de TDP-43. El kit incluirá aptámeros biotinilados, un sistema de detección basado en fluorescencia o quimioluminiscencia y un ensayo modular compatible con ELISA, lo que permitirá una detección no invasiva, escalable y rentable. En conjunto, el objetivo del proyecto es mejorar el diagnóstico temprano de la ELA.

Objetivo

The AptALS project aims to develop a highly sensitive and scalable RNA aptamer-based kit for detecting TDP-43 aggregates, a key biomarker in ALS. The kit consists of 3 main components: (i) biotinylated RNA aptamers that selectively bind aggregated TDP-43, (ii) a detection system (fluorescence or chemiluminescence) to quantify binding events, and (iii) a modular assay format compatible with ELISA-like workflows, allowing seamless integration into clinical laboratories. By leveraging our patented aptamers, we will validate their performance in a standardized detection assay, ensuring clinical robustness. Unlike conventional antibody-based methods, RNA aptamers offer superior specificity and adaptability, enabling non-invasive, early-stage ALS detection. This innovation fills a critical gap in ALS diagnostics, replacing invasive lumbar punctures and costly neuroimaging with a cost-effective, scalable alternative. The AptALS project will focus on three key objectives: (i) assay validation, (ii) optimization of detection methods (fluorescence vs. chemiluminescence), and (iii) benchmarking with ALS patient samples. The project is led by a multidisciplinary team with expertise in biophysics, molecular biology, and computational modeling, supported by IIT’s state-of-the-art genomics, proteomics, and microscopy facilities to ensure technical rigor and scalability. Beyond its scientific impact, AptALS delivers significant societal and economic benefits. Early ALS detection can enable timely intervention, improve patient care, and reduce healthcare costs. The diagnostic kit is designed for B2B distribution, targeting hospitals, diagnostic laboratories, and pharmaceutical companies for clinical trials and patient stratification. Positioned at the forefront of neurodegenerative disease diagnostics, AptALS is poised for strong commercial adoption, bridging the gap between research and real-world clinical application, fostering innovation, and advancing ALS care.