Leveraging Modifier Genes & Molecular Signatures to Stratify Fast Vs Slow Progressors in ALS

  • Characterizing variants such as those in UNC13A that shape both ALS susceptibility and disease trajectory, influencing rate of decline and survival
  • Identifying emerging risk and modifier genes through integrated GWAS, WGS, splicing-QTL, and rare-variant analyses to illuminate new mechanisms driving heterogeneity
  • Improving progression modeling by addressing limitations of ALSFRS-R, incorporating survival data, and integrating biomarkers like longitudinal neurofilament levels to better link genotype with phenotype
  • Prioritizing genetically validated progression modifiers as compelling targets for disease-modifying therapies with broad patient impact