Abstract #1075

3T MRI and MR Spectroscopy of a Feline Model of Sandhoff Disease After AAV-Mediated Gene Therapy

Heather L. Gray-Edwards¹, Nouha Salibi², Diane Wilson¹, Ashley Randle¹, Ronald J. Beyers³, Thomas Stewart Denney³, Ravi T. Seethamraju², Shumin Wang³, Xiaotong Sun³, Allison M. Bradbury⁴, Victoria J. McCurdy⁴, Aime K. Johnson⁵, Nancy Cox¹, Douglas R. Martin,¹⁴

¹Scott-Ritchey Research Center, Auburn University, Auburn, Al, United States; ²MR R&D, Siemens Healthcare, Malvern, PA, United States; ³Department of Electrical and Computer Engineering, Auburn Univeristy, Auburn, AL, United States; ⁴Anatomy, Physiology and Pharmacology, Auburn University, Auburn, Al, United States; ⁵Clinical Sciences, Auburn University, Auburn, Al, United States

Sandhoff disease (SD) is a form of GM2 gangliosidosis in humans that is untreatable and fatal by 5 years of age. Thee feline SD model has the same subunit mutation as Sandhoff patients. AAV2/rh8 vectors expressing feline hexosaminidase subunits were injected bilaterally into the thalamus and deep cerebellar nuclei of SD cats. MR images and Magnetic Resonance Spectroscopy (MRS) data were acquired on a 3 Tesla MAGNETOM Verio scanner. Untreated SD cat shows gray:white matter inversion and elevations of brain metabolites. Gene replacement in the feline SD model results in restoration of both brain architecture and metabolites.