Spinal Muscular Atrophy (SMA) and Haloperidol as a Potential Therapeutic

This study explores Haloperidol (HALO), a classical antipsychotic, as a potential Spinal Muscular Atrophy (SMA) treatment due to its ability to modulate SMN2 splicing and enhance SMN expression. Using the delta 7 SMA mouse model, HALO (0.5 mg/kg/day) was administered from postnatal day 2 (P2) to day 12 (P12), followed by histological, molecular, and RNA-seq analyses of spinal cord and muscle tissues to evaluate treatment effects. For RNA sequencing, total RNA was extracted from spinal cord (HALO n=4, VHL n=5) and quadriceps (HALO n=4, VHL n=4), with libraries prepared using the Illumina TruSeq Stranded mRNA Kit and sequenced on a NovaSeq 6000 S1 platform (2x100 bp, 50M reads/sample). RNA-seq data revealed extensive expression and splicing changes in spinal cords, including direct SMN targets, suggesting enhanced SMN activity, while quadriceps showed hundreds of differentially expressed genes but no major splicing alterations. These findings highlight HALO's potential as an alternative SMA therapeutic, demonstrating its ability to modulate transcription across tissues, with pronounced effects on splicing in the nervous system.