Cognitive Abilities of Dogs with Mucopolysaccharidosis I: Learning and Memory

Mucopolysaccharidosis I (MPS I) results from a deficiency of a lysosomal enzyme, alpha-L-iduronidase (IDUA). IDUA deficiency leads to glycosaminoglycan (GAG) accumulation resulting in cellular degeneration and multi-organ dysfunction. The primary aims of this pilot study were to determine the feasibility of cognitive testing MPS I affected dogs and to determine their non-social cognitive abilities with and without gene therapy. Fourteen dogs were tested: 5 MPS I untreated, 5 MPS I treated, and 4 clinically normal. The treated group received intrathecal gene therapy as neonates to replace the IDUA gene. Cognitive tests included delayed non-match to position (DNMP), two-object visual discrimination (VD), reversal learning (RL), attention oddity (AO), and two-scent discrimination (SD). Responses were recorded as correct, incorrect, or no response, and analyzed using mixed effect logistic regression analysis. Significant differences were not observed among the three groups for DNMP, VD, RL, or AO. The MPS I untreated dogs were excluded from AO testing due to failing to pass acquisition of the task, potentially representing a learning or executive function deficit. The MPS I affected group (treated and untreated) was significantly more likely to discriminate between scents than the normal group, which may be due to an age effect. The normal group was comprised of the oldest dogs, and a mixed effect logistic model indicated that older dogs were more likely to respond incorrectly on scent discrimination. Overall, this study found that cognition testing of MPS I affected dogs to be feasible. This work provides a framework to refine future cognition studies of dogs affected with diseases, including MPS I, in order to assess therapies in a more comprehensive manner.