Cognitive Abilities of Dogs with Mucopolysaccharidosis I: Learning and Memory

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.

Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology

“…Behavioral and cognitive defects have been observed in MPS I mice [137][138][139][140] but skeletal abnormalities and sensatory deficiencies need to be considered when analyzing the results [141]. No cognitive deficits were found in MPS I dogs [142].…”

Differences in MPS I and MPS II Disease Manifestations

“…However, species-specific disease manifestations need to be considered. Canine animal models for MPS I tend to show milder manifestations compared to humans afflicted by the disease [170][171][172]. The introduction of exact mutations in mouse models provides insights into the genetics of the disease [173,174].…”

Clinical and pathological characterization of ophthalmic disease in a canine model of mucopolysaccharidosis type I

“…The natural disease course observed in these animals is such that limb and joint abnormalities as well as liver and cardiac disease develop first at approximately 3-6 months of age, with ocular and neurologic abnormalities developing at approximately 10 months of age. 17,18 After approximately 1 year of age these dogs develop progressive corneal opacity and succumb to their somatic disease at approximately 3 years of age. 7,9,17,18 Dogs were euthanized by intravenous sodium pentobarbital overdose.…”

“…17,18 After approximately 1 year of age these dogs develop progressive corneal opacity and succumb to their somatic disease at approximately 3 years of age. 7,9,17,18 Dogs were euthanized by intravenous sodium pentobarbital overdose. Ages and disease status of dogs examined clinically and/or histologically are as follows; S1).…”