Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A female Japanese domestic shorthair cat showed gait abnormality at 5 months of age, and head shaking and tremor became apparent from 6 months of age. Serum biochemistry at 13 months of age revealed markedly elevated ALT and ALP. The cat died at 16 months of age. Histopathologic examination revealed prominent cytoplasmic swelling of neurons with accumulation of yellowish pigments. The storage pigments stained positively with periodic acid Schiff reaction, Schmorl method, and Oil red O stain. Ultrastructurally, the neuronal storage consisted of aggregates of dense materials, similar to the granular osmiophilic deposits in infantile ceroid-lipofuscinosis in humans. Hepatocytes were markedly swollen and contained faintly eosinophilic inclusion. To our knowledge this case is the sixth case of feline ceroid-lipofuscinosis, which is characterized by granular osmiophilic dense bodies in the neurons and prominent involvement of hepatocytes.
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PMID:Neuronal ceroid-lipofuscinosis in a Japanese domestic shorthair cat. 1949 97

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.
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PMID:Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression. 2807 62