Translation-specific disruption of Col1a1 expression in multiple models of Spinal Muscular Atrophy can be rescued by Risdiplam.

The preprint operates within the dominant paradigm of molecular biology and genetics as applied to understanding and treating Spinal Muscular Atrophy (SMA). This paradigm emphasizes the role of SMN protein deficiency as the central cause of SMA and focuses on therapies that increase SMN levels.

This preprint investigates the translational alterations caused by SMN deficiency in SMA, building upon the established understanding of SMN's role in RNA metabolism and translation. The research identifies COL1A1 as a potential translational biomarker for SMA, correlating with disease severity and response to treatment in pediatric patients. This adds to the existing body of knowledge within the current paradigm, refining our understanding of SMA pathogenesis and potential therapeutic avenues. The study does not challenge the existing paradigm but rather contributes to the ongoing "puzzle-solving" activity characteristic of normal science, exploring the specifics of how SMN deficiency affects cellular processes and how these effects might be mitigated. While the identification of COL1A1 as a potential biomarker is novel, it doesn't represent a paradigm shift but rather a refinement of existing diagnostic and prognostic tools within the current framework. Since this is a preprint, there is a possibility of model drift, as the findings are not yet peer-reviewed and may be subject to revision. It seems unlikely, though possible, that the findings represent a Model Crisis. This would require the proposed biomarker to consistently fail to predict disease severity or treatment response, or for the findings to contradict other established aspects of SMA biology in a way that cannot be easily reconciled.