The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1
Myotonic dystrophy type 1(DM1) is a progressive, multisystemic disorder caused by a CTG repeat expansion in the DMPK 3' UTR that leads to global dysregulation of alternative splicing. As the decline in physical function is slow, a biomarker measuring the association between RNA mis-splicing and weakness may be helpful in predicting future function. Here we replicate the development of the Splice Index (SI) as a potential biomarker. Adults with DM1 had muscle biopsies of the tibialis anterior at baseline (n = 46) and 3 months (n = 34) along with measures of strength and physical function. The SI was reliable across technical replicates. It had significant associations to measures of ankle dorsiflexion strength (r = -0.697) that improved when comparing the baseline SI to the 3-month ankle dorsiflexion strength (r = -0.78). A linear regression model demonstrates that the combination of baseline ankle dorsiflexion strength and SI is highly predictive of the strength at 3 months (adjusted R2 = 0.83). In combination these results indicate the SI is reliable, accurately captures associations with physical strength and mobility, and is predictive of future function.