Cognitive Abilities of Dogs with Mucopolysaccharidosis I: Learning and Memory

SIMPLE SUMMARY: Lysosomes are cell organelles that contain enzymes that break down large molecules to be recycled or discarded. When lysosomal enzymes fail to perform this function, molecules become trapped and cause cellular destruction. Mucopolysaccharidosis I (MPS I) is a rare disease that occurs in dogs and humans due to a deficiency of the lysosomal enzyme, alpha-L-iduronidase. Humans affected with MPS I experience mild to severe clinical signs in facial features, skeletal changes, cognitive decline, and heart, liver, and respiratory disease. Similarly, MPS I in dogs also cause facial changes, musculoskeletal degeneration, spinal cord compression, and heart and liver disease. However, the cognitive ability in dogs affected with MPS I has not been investigated. The purpose of this pilot study was to determine the feasibility of conducting cognitive tests on MPS I affected dogs and their cognitive abilities. Three groups of dogs were tested: MPS I untreated, MPS I treated, and clinically normal. Dogs were successfully trained to perform the cognitive tests. Differences in their ability to reach the criterion was evident in attention oddity and scent discrimination tests. This study found cognition testing of dogs affected with MPS I to be feasible and recommend future studies focus on a single cognitive domain at a time. ABSTRACT: 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.