Transcriptome assessment of the Pompe (Gaa-/-) mouse cervical cord confirms widespread neuropathology.

The only FDA approved therapy for Pompe is directed at correcting skeletal and cardiac muscle pathology, however, clinical and animal model data show strong histological evidence for a neurological disease component. While neuronal cell death and neuroinflammation are prominent in many lysosomal disorders, these processes have not been evaluated in Pompe disease. There is also no information available regarding the impact of Pompe disease on the fundamental pathways associated with synaptic communication. We used microarrays to gain insight regarding pathogenetic signaling pathways that might contribute to neuropathology in Pompe (Gaa-/-) mice. To test whether systemic absence of GAA protein activated signalling pathways associated with neuropathology, genomic data (Affymetrix Mouse Gene Array 2.0ST) from the mid-cervical spinal cord in 6-and 16-mo old Pompe (Gaa-/-) were evaluated.