Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression.

CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.

Computed tomographic findings in 44 dogs and 10 cats with grass seed foreign bodies.

OBJECTIVE: To supplement recent reports of computed tomographic (CT) findings in dogs and cats with grass seed foreign bodies. METHODS: Retrospective review of cases that had CT scan and subsequent retrieval of a grass seed during the same period of hospitalisation from a site included in the scan. RESULTS: Records of 44 dogs and 10 cats were reviewed. Most were presented in the months July to December. Median duration of clinical signs was 4 weeks (range 2 days to 2 years). The most frequent clinical signs were soft tissue swelling (30% cases), coughing (28%), sneezing (28%) and discharge (26%). Grass seeds were retrieved from the thorax (35% cases), nasal cavity (31%), ear (7%), other sites in the head and neck (22%), sublumbar muscles (2%) and pelvic limb (2%). The grass seed was visible in CT images in 10 (19%) cases. Secondary lesions were visible in CT images of 52 (96%) cases, including collection of exudate (37%), abscess (24%), enlarged lymph nodes (22%) and pulmonary consolidation (20%). CT images appeared normal in 4% animals. CLINICAL SIGNIFICANCE: Grass seeds within the respiratory tract are frequently visible in CT images, but in general CT appears to be more useful for localisation of secondary lesions than as a method of definite diagnosis.