Lingual EMG activity in Pompe rats indicates impaired motor unit recruitment

Pompe disease (PD) is an autosomal recessive disorder caused by mutations in the gene encoding acid alpha-glucosidase (GAA), leading to lysosomal glycogen accumulation and progressive neuromuscular dysfunction. Respiratory dysfunction is prominent in both infantile and late-onset PD, often progressing to respiratory failure. Patients often exhibit lingual weakness, dysphagia, feeding difficulties, and, in adults, obstructive sleep apnea. These deficits are consistent with tongue motor dysfunction and often persist despite ongoing enzyme replacement therapy. Prior studies in PD patients and Pompe mouse models (Gaa -/- ) have demonstrated hypoglossal (XII) motoneuron histopathology and neurodegeneration. We recently described a Gaa -/- rat model of PD that also demonstrates cardiorespiratory impairments (PMID: 40518673). Herein, we used the Gaa -/- rat model to test the hypothesis that lingual electromyogram (EMG) activation is reduced during spontaneous breathing. Intralingual (genioglossus) EMG activity was recorded using bipolar hook-style intramuscular electrodes placed bilaterally into the tongue in anesthetized, spontaneously breathing (2.5% isoflurane in 50/50% O 2 /N 2 ) 12-month-old Gaa -/- and wild-type (WT, Sprague-Dawley) rats (n=3-4/group). Recordings were performed in a single acute terminal preparation to assess changes in tongue muscle activity before and after bilateral vagotomy. Prior to vagotomy, Gaa -/- rats exhibited a markedly reduced mean peak inspiratory EMG burst amplitude compared to WT (Gaa -/- : 0.11±0.02% vs. WT:0.44±0.16% (% post-vagotomy maximal amplitude)). This difference was no longer apparent following vagotomy (Gaa -/- : 0.76±0.10% vs. WT:0.81±0.03%). Power spectral analyses of EMG activity demonstrated a reduction in EMG power across 250-1000Hz in Gaa -/- rats compared to WT both before and after bilateral vagotomy. This decrease in power across all frequencies, combined with reduced peak amplitude, indicates weakened neural drive to the tongue that is likely reflective of diminished recruitment of functional motor units. These preliminary findings provide a foundation for ongoing development and evaluation of lingual-directed AAV gene therapy, with the aim of improving upper airway function and associated behaviors in individuals with Pompe Disease. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.