Raffaele Dubbioso

Introduction: Riluzole is available as tablets (T), oral suspension (OS), and orodispersible film (OF), but comparative real-world data on tolerability, administration burden, and patient-reported experience are limited. Methods: In this longitudinal study, 138 patients with amyotrophic lateral sclerosis (ALS) were evaluated at baseline (79 OF, 21 OS, 38 T) and 97 were reassessed after a median of 3.9 months. Results: OS-treated patients had longer disease duration and greater functional impairment than OF or T (p < 0.001), reflecting preferential use in more advanced disease. Oral numbness was more frequent with OF than OS or T (54.4% vs. 14.3% vs. 13.2%; p < 0.001) and decreased during follow-up (42.3%–28.9%; p = 0.016), partly because patients reporting it switched away from OF. OF use (adjusted OR 10.55 vs. T, p < 0.001) and female sex (OR 2.59, p = 0.035) were independently associated with higher, and older age with lower, odds of an adverse event at baseline (OR 0.43 per 10-year increment, p < 0.001); at 3-month follow-up, OF remained the strongest formulation-related predictor (OR 5.42, p = 0.024), while an adverse event already present at baseline was itself the strongest predictor of one at follow-up (OR 5.11, p = 0.006). Dysphagia was associated with tablet manipulation (OR 7.19, p = 0.034). Differences among formulations concerned packaging convenience and independent self-administration rather than overall satisfaction, and lower disease severity was weakly associated with higher satisfaction regardless of formulation (ρ = 0.21, p = 0.015). Formulation persistence among reassessed patients was high (85.6%), and most patients who left OF had anticipated this intention at baseline. Discussion: The three riluzole formulations are used in clinically distinct ALS populations and differ in tolerability and usability rather than overall satisfaction, and a prior adverse event marks persisting risk. Formulation choice should be individualized and periodically reassessed as disease progresses.

CircRNAs are covalently closed ncRNAs originating through back splicing; their expression is finely regulated, displaying specific patterns across different cell types, tissues, and developmental stages. While the molecular functions of circRNAs are not completely elucidated, their regulatory involvement in physiological processes is well established, alongside their dysregulation in several human disorders. These features, together with their higher stability compared to other ncRNAs, make this class of molecules promising theragnostic agents, particularly in biomarker discovery. Accordingly, it is crucial to develop and standardize experimental strategies that improve circRNA analysis, ensuring accurate and effective isolation of these molecules. In biomarker discovery, selecting the appropriate biological matrix is critical; whole blood is often preferred for its accessibility and minimally invasive collection. Because circRNAs are present in human peripheral blood and show promise as disease theragnostic biomarkers, we established a preliminary workflow tailored to isolate and analyze circRNAs from whole blood. The promising effectiveness and robustness of this workflow were demonstrated by qPCR analysis, suggesting highly reproducible detection and reliability in isolating and analyzing circRNAs. This, together with their stability and specific expression profiles, supports the utility of circRNAs in biomarker discovery and advanced circRNA research and contributes to accelerating their future integration into theragnostic applications in clinical settings.

This scientific commentary refers to ‘King’s stages of amyotrophic lateral sclerosis: an 18F-FDG-PET study of brain connectivity’, by Di Pede et al. (https://doi.org/10.1093/brain/awag159).

Background and ObjectivesPhosphorylated TAR DNA-binding protein 43 (pTDP-43) is the pathologic hallmark of amyotrophic lateral sclerosis (ALS), yet no peripheral premortem biomarker is available. W...

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder for which despite its severity, no validated biomarker currently exists to support early diagnosis, limiting therapeutic effectiveness and patient survival. In this context, mathematical modeling therefore becomes essential: it allows us to maximize the information obtainable from a limited number of samples, identify patterns that may not be directly observable, and estimate the relative contribution of different molecular markers to ALS progression. In this work, we propose methods for qualitatively and quantitatively evaluating the relevance of selected biomarkers in ALS classification and disease-state identification and laying the foundations for the definition of a protocol useful for constructing “digital twins” of the entire process of study, diagnosis, and treatment of the disease from the perspective of innovative precision medicine.