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, Nancy Cox1,
Douglas R. Martin4
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
Tay-Sachs Disease (TSD) is a form of GM2 gangliosidosis in humans that is untreatable and fatal by 5 years of age. The ovine TSD model has the same subunit mutation as Tay-Sachs patients. AAV2/rh8 vectors expressing ovine hexosaminidase subunits were injected in the lateral ventricle and bilaterally into the thalamus of TSD sheep. MR images and Magnetic Resonance Spectroscopy (MRS) data were acquired on a 3 Tesla MAGNETOM Verio scanner. Untreated TSD sheep show gray:white matter isointensity and elevations of brain metabolites. Gene replacement in the ovine TSD model results in restoration of both brain architecture and metabolites.