Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs

World Health Organization. Genes and human disease. http://www.who.int/genomics/public/geneticdiseases/en/index2.html. Guan, 2016, Gene therapy in monogenic congenital myopathies, Methods, 99, 91, 10.1016/j.ymeth.2015.10.004 Jungbluth, 2008, Centronuclear (myotubular) myopathy, Orphanet J. Rare Dis., 3, 26, 10.1186/1750-1172-3-26 Savarese, 2016, Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers, Neuromuscul. Disord., 26, 292, 10.1016/j.nmd.2016.02.004 Laporte, 1998, Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human, Hum. Mol. Genet., 7, 1703, 10.1093/hmg/7.11.1703 Lawlor, 2016, Skeletal muscle pathology in X-linked myotubular myopathy: review with cross-species comparisons, J. Neuropathol. Exp. Neurol., 75, 102, 10.1093/jnen/nlv020 Childers, 2014, Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy, Sci. Transl. Med., 6, 220ra10, 10.1126/scitranslmed.3007523 Lawlor, 2013, Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy, Hum. Mol. Genet., 22, 1525, 10.1093/hmg/ddt003 Snyder, 2015, Validity of a neurological scoring system for canine X-linked myotubular myopathy, Hum. Gene Ther. Clin. Dev., 26, 131, 10.1089/humc.2015.049 Goddard, 2014, Gait characteristics in a canine model of X-linked myotubular myopathy, J. Neurol. Sci., 346, 221, 10.1016/j.jns.2014.08.032 Goddard, 2015, Muscle pathology, limb strength, walking gait, respiratory function and neurological impairment establish disease progression in the p.N155K canine model of X-linked myotubular myopathy, Ann. Transl. Med., 3, 262 Herman, 1999, Medical complications in long-term survivors with X-linked myotubular myopathy, J. Pediatr., 134, 206, 10.1016/S0022-3476(99)70417-8 Goddard, 2012, Establishing clinical end points of respiratory function in large animals for clinical translation, Phys. Med. Rehabil. Clin. N. Am., 23, 75, 10.1016/j.pmr.2011.11.017 Sisson, 1991, Changes in linear dimensions of the heart, relative to body weight, as measured by M-mode echocardiography in growing dogs, Am. J. Vet. Res., 52, 1591 Buj-Bello, 2008, AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis, Hum. Mol. Genet., 17, 2132, 10.1093/hmg/ddn112 Shen, 2013, Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency, J. Biol. Chem., 288, 28814, 10.1074/jbc.M113.482380 Asokan, 2010, Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle, Nat. Biotechnol., 28, 79, 10.1038/nbt.1599 Nathwani, 2014, Our journey to successful gene therapy for hemophilia B, Hum. Gene Ther., 25, 923, 10.1089/hum.2014.2540 Nathwani, 2011, Adenovirus-associated virus vector-mediated gene transfer in hemophilia B, N. Engl. J. Med., 365, 2357, 10.1056/NEJMoa1108046 Nathwani, 2007, Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates, Blood, 109, 1414, 10.1182/blood-2006-03-010181 Wang, 2011, Muscle-directed gene therapy for hemophilia B with more efficient and less immunogenic AAV vectors, J. Thromb. Haemost., 9, 2009, 10.1111/j.1538-7836.2011.04491.x Nietupski, 2011, Systemic administration of AAV8-α-galactosidase A induces humoral tolerance in nonhuman primates despite low hepatic expression, Mol. Ther., 19, 1999, 10.1038/mt.2011.119 Bell, 2011, Inverse zonation of hepatocyte transduction with AAV vectors between mice and non-human primates, Mol. Genet. Metab., 104, 395, 10.1016/j.ymgme.2011.06.002 Yue, 2015, Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus, Hum. Mol. Genet., 24, 5880, 10.1093/hmg/ddv310 Romero, 2010, Centronuclear myopathies: a widening concept, Neuromuscul. Disord., 20, 223, 10.1016/j.nmd.2010.01.014 Beggs, 2010, MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers, Proc. Natl. Acad. Sci. USA, 107, 14697, 10.1073/pnas.1003677107 Hurlbut, 2010, Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy, Mol. Ther., 18, 1983, 10.1038/mt.2010.175 Nathwani, 2006, Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver, Blood, 107, 2653, 10.1182/blood-2005-10-4035 Grange, 2012, Muscle function in a canine model of X-linked myotubular myopathy, Muscle Nerve, 46, 588, 10.1002/mus.23463 Lang, 2015, Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging, Eur. Heart J. Cardiovasc. Imaging, 16, 233, 10.1093/ehjci/jev014 Kornegay, 1999, Contraction force generated by tarsal joint flexion and extension in dogs with golden retriever muscular dystrophy, J. Neurol. Sci., 166, 115, 10.1016/S0022-510X(99)00118-5 Childers, 2011, In vivo canine muscle function assay, J. Vis. Exp., e2623 Le Guiner, 2014, Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients, Mol. Ther., 22, 1923, 10.1038/mt.2014.151 Brewer, 1994, Volume 2, 123 Bostock, 2011, D3: data-driven documents, IEEE Trans. Vis. Comput. Graph., 17, 2301, 10.1109/TVCG.2011.185 Boutin, 2010, Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors, Hum. Gene Ther., 21, 704, 10.1089/hum.2009.182 Monteilhet, 2011, A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8, Mol. Ther., 19, 2084, 10.1038/mt.2011.108 Meliani, 2015, Determination of anti-adeno-associated virus vector neutralizing antibody titer with an in vitro reporter system, Hum. Gene Ther. Methods, 26, 45, 10.1089/hgtb.2015.037 Veron, 2012, Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors, J. Immunol., 188, 6418, 10.4049/jimmunol.1200620 Meng, 2014, Tissue triage and freezing for models of skeletal muscle disease, J. Vis. Exp., e51586 Lawlor, 2014, Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice, Am. J. Pathol., 184, 1831, 10.1016/j.ajpath.2014.03.003 Liu, 2013, Automated fiber-type-specific cross-sectional area assessment and myonuclei counting in skeletal muscle, J. Appl. Physiol., 115, 1714, 10.1152/japplphysiol.00848.2013 Dastgir, 2016, Common data elements for muscle biopsy reporting, Arch. Pathol. Lab. Med., 140, 51, 10.5858/arpa.2014-0453-OA Team, R.C. (2015). A language and environment for statistical computing. R Foundation for Statistical Computing, http://www.R-project.org/. Seshan, V.E. (2016). clinfun: clinical trial design and data analysis functions. https://cran.r-project.org/package=clinfun.