Abstract # 13382 Event # 214:

Scheduled for Saturday, August 24, 2019 01:45 PM-02:00 PM: (Room 309) Oral Presentation


DEVELOPMENT OF THE BABOON (P. ANUBIS) AS A NON-HUMAN PRIMATE (NHP) MODEL FOR COCHLEAR GENE THERAPY

S. P. Francis1, M. J. McKenna1,3,4, E. A. Clemmons2, R. Ng1, W. F. Sewell1,3,4, E. J. Simons1 and M. D. Valero1,3
1Akouos, Boston, MA 02111, USA, 2Southwest National Primate Research Center, Texas Biomedical Research Center, 3Massachussetts Eye and Ear, 4Harvard Medical School
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     Cochlear gene therapy is a promising modality to address genetic and acquired hearing loss. Previous work in genetically deaf transgenic mice demonstrated that synthetic adeno-associated viral Anc80 vectors can rescue cochlear function by delivering healthy gene copies to cochlear inner hair cells (IHCs). Intermediary models that are anatomically, developmentally, and immunogenically more similar to humans are important for translation to the clinic. Andres-Mateos et al. (2019) and Francis et al. (2019) demonstrated efficient IHC transduction with Anc80 in M. mulatta and M. fascicularis, respectively, including macaques with low pre-existing immunity against Anc80. Here, we extend these findings to the baboon, which has a cochlear volume twice that of the macaque and approximately two-thirds of the human. Baboons with normal cochlear function were included in the study. Using an optimized surgical approach, we injected Anc80 vector encoding a green-fluorescent protein (GFP) intracochlearly in two baboons with low or moderate pre-existing immunity against Anc80. Following a 3-week survival, serum and CSF were collected, and cochleae were harvested. Fluorescent imaging revealed GFP expression in IHCs along the full length of the cochlear spiral. These data demonstrate efficient transgene expression in large NHP cochleae, provide preliminary evidence that moderate serum neutralizing (NAb) levels do not inhibit IHC transduction, and support intracochlear administration of Anc80 as a promising strategy to evaluate in clinical trials.