Bony Abnormalities in Feline Models of GM2 Gangliosidosis

Abstract

This study seeks to explore and quantify bony deformities in feline models affected with GM2 gangliosidosis with emphasis on long bones and cervical vertebrae, based on previous diagnostics exhibiting cervical spinal cord compression, luxating coxofemoral and patellar joints, and tibial bowing. We hypothesized that vertebral and long limb abnormalities initiate spinal cord compression and limb weakness, respectively. The study design was comprised of GM2 cats treated intracranially via adeno-associated virus (AAV) gene-therapy by thalami and intracerebroventricular (ICV) injections, GM2 untreated, and sex and age-matched normal and carrier cats. Whole body computed tomography (CT) scans were performed on GM2 affected and normal subjects. Scans were analyzed using Mimics Materialise Software and limb bones were printed using a 3D printer to obtain length measurements. Limb samples were sent to Louisiana State University for micro-CT analysis, and results were consistent with conventional CT findings. Significant differences were found in nearly all bone measurements, suggesting that bony abnormalities contribute to limb weaknesses. Vertebral column deformities did not reach significance, though spinal cord compression is clearly seen at necropsy in some animals. Future studies will be conducted to test alleviation of peripheral disease manifestations such as bony abnormalities.