@article{demaster_luo_curtis_williams_landau_drake_kozink_bird_crane_sun_et al._2012, title={Long-Term Efficacy Following Readministration of an Adeno-Associated Virus Vector in Dogs with Glycogen Storage Disease Type Ia}, volume={23}, ISSN={["1557-7422"]}, DOI={10.1089/hum.2011.106}, abstractNote={Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated with double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration of an AAV9 pseudotyped (AAV2/9) vector to seven consecutive GSD-Ia neonates prevented hypoglycemia during fasting for up to 8 hr; however, efficacy eventually waned between 2 and 30 months of age, and readministration of a new pseudotype was eventually required to maintain control of hypoglycemia. Three of these dogs succumbed to acute hypoglycemia between 7 and 9 weeks of age; however, this demise could have been prevented by earlier readministration an AAV vector, as demonstrated by successful prevention of mortality of three dogs treated earlier in life. Over the course of this study, six out of nine dogs survived after readministration of an AAV vector. Of these, each dog required readministration on average every 9 months. However, two were not retreated until >34 months of age, while one with preexisting antibodies was re-treated three times in 10 months. Glycogen content was normalized in the liver following vector administration, and G6Pase activity was increased in the liver of vector-treated dogs in comparison with GSD-Ia dogs that received only with dietary treatment. G6Pase activity reached approximately 40% of normal in two female dogs following AAV2/9 vector administration. Elevated aspartate transaminase in absence of inflammation indicated that hepatocellular turnover in the liver might drive the loss of vector genomes. Survival was prolonged for up to 60 months in dogs treated by readministration, and all dogs treated by readministration continue to thrive despite the demonstrated risk for recurrent hypoglycemia and mortality from waning efficacy of the AAV2/9 vector. These preclinical data support the further translation of AAV vector-mediated gene therapy in GSD-Ia.}, number={4}, journal={HUMAN GENE THERAPY}, author={Demaster, Amanda and Luo, Xiaoyan and Curtis, Sarah and Williams, Kyha D. and Landau, Dustin J. and Drake, Elizabeth J. and Kozink, Daniel M. and Bird, Andrew and Crane, Bayley and Sun, Francis and et al.}, year={2012}, month={Apr}, pages={407–418} }
 @article{crane_luo_demaster_williams_kozink_zhang_brown_pinto_oka_sun_et al._2012, title={Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia}, volume={19}, ISSN={["0969-7128"]}, DOI={10.1038/gt.2011.86}, abstractNote={Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.}, number={4}, journal={GENE THERAPY}, author={Crane, B. and Luo, X. and Demaster, A. and Williams, K. D. and Kozink, D. M. and Zhang, P. and Brown, T. T. and Pinto, C. R. and Oka, K. and Sun, F. and et al.}, year={2012}, month={Apr}, pages={443–452} }
 @article{koeberl_pinto_sun_li_kozink_benjamin_demaster_kruse_vaughn_hillman_et al._2008, title={AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia}, volume={16}, ISSN={["1525-0016"]}, DOI={10.1038/mt.2008.15}, abstractNote={Glycogen storage disease type Ia (GSD-Ia) profoundly impairs glucose release by the liver due to glucose-6-phosphatase (G6Pase) deficiency. An adeno-associated virus (AAV) containing a small human G6Pase transgene was pseudotyped with AAV8 (AAV2/8) to optimize liver tropism. Survival was prolonged in 2-week-old G6Pase (-/-) mice by 600-fold fewer AAV2/8 vector particles (vp), in comparison to previous experiments involving this model (2 x 10(9) vp; 3 x 10(11) vp/kg). When the vector was pseudotyped with AAV1, survival was prolonged only at a higher dose (3 x 10(13) vp/kg). The AAV2/8 vector uniquely prevented hypoglycemia during fasting and fully corrected liver G6Pase deficiency in GSD-Ia mice and dogs. The AAV2/8 vector has prolonged survival in three GSD-Ia dogs to >11 months, which validated this strategy in the large animal model for GSD-Ia. Urinary biomarkers, including lactate and 3-hydroxybutyrate, were corrected by G6Pase expression solely in the liver. Glycogen accumulation in the liver was reduced almost to the normal level in vector-treated GSD-Ia mice and dogs, as was the hepatocyte growth factor (HGF) in GSD-Ia mice. These preclinical data demonstrated the efficacy of correcting hepatic G6Pase deficiency, and support the further preclinical development of AAV vector-mediated gene therapy for GSD-Ia.}, number={4}, journal={MOLECULAR THERAPY}, author={Koeberl, Dwight D. and Pinto, Carlos and Sun, Baodong and Li, Songtao and Kozink, Daniel M. and Benjamin, Daniel K., Jr. and Demaster, Amanda K. and Kruse, Meghan A. and Vaughn, Valerie and Hillman, Steven and et al.}, year={2008}, month={Apr}, pages={665–672} }
 @article{pinto_kozink_2008, title={Simplified hypoosmotic swelling testing (HOST) of fresh and frozen-thawed canine spermatozoa}, volume={104}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2007.07.005}, abstractNote={The clinical use of the hypoosmotic swelling test (HOST) to identify spermatozoa with a functional intact membrane has been reported for humans and domestic species, including the dog. Currently, it is recommended that canine spermatozoa be incubated with the hypoosmotic solution for periods that range from 30 to 60 min. In an attempt to simplify the test, it was hypothesized that the degree of the hypoosmotic response at 1 min of incubation would not be different from the response documented at 60 min after incubation in the hypoosmotic solution at 37 degrees C. The hypoosmotic response of spermatozoa from 50 fresh and 16 frozen-thawed semen samples obtained from 22 adult dogs was recorded at 1 and 60 min of incubation. There were no significant differences between the hypoosmotic response recorded at 1 and 60 min for all evaluated semen samples (P>0.10). The hypoosmotic response recorded for canine spermatozoa from fresh semen samples were greater than that recorded for spermatozoa from frozen-thawed semen, both at 1 min (86.2% compared with 65.2%; P<0.001) and 60 min (85.6% compared with 61.8%; P<0.001). Based on the results of this study, it is recommended to decrease the incubation time of the HOST for canine spermatozoa to as short a period as 1 min. This incubation time should encourage the application of this relatively simple and inexpensive test of canine sperm membrane function in a clinical setting.}, number={2-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Pinto, C. R. F. and Kozink, D. M.}, year={2008}, month={Mar}, pages={450–455} }