RNA-centric approaches in amyotrophic lateral sclerosis: prospects for future therapeutics

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by profound clinical and molecular heterogeneity, which has substantially hindered the development of effective therapies. Significant advances in ALS research have been driven by the study of RNA biology, together with the implementation of advanced transcriptomic technologies and artificial intelligence-based algorithms, which are assuming a transformative role in reshaping the field.

We discuss how genome-wide expression profiling enables the identification of molecular signatures for drug discovery and repurposing, facilitates the stratification of patients into biologically distinct subtypes for more refined clinical trials, and guides the development of novel nucleic acid-based therapies. Furthermore, we explore the potential of transcriptomics to identify molecular vulnerabilities during pre-symptomatic stages, paving the way for early intervention.

The convergence of transcriptomics and artificial intelligence is poised to fundamentally redefine ALS, transforming it from a single clinical entity into a spectrum of molecularly defined disorders, each potentially amenable to targeted therapeutic intervention. While challenges in translating high-dimensional data into clinical practice remain, the integration of transcriptomics with advanced computational tools promises to accelerate the transition toward a new era of personalized medicine in ALS.