Long-term neurological effects of bone marrow transplantation in a canine lysosomal storage disease

• Published in: Pediatric research Vol. 24; no. 3; pp. 347 - 352
• Main Authors: SHULL, R. M, BREIDER, M. A, CONSTANTOPOULOS, G. C
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.09.1988
• Subjects: Animals; Biological and medical sciences; Bone Marrow Transplantation; Cerebral Cortex - enzymology; Cerebral Cortex - pathology; Cerebral Cortex - ultrastructure; Dog Diseases - pathology; Dog Diseases - surgery; Dogs; Errors of metabolism; Glycosaminoglycans - analysis; Iduronidase - deficiency; Iduronidase - metabolism; Lipids (lysosomal enzyme disorders, storage diseases); Medical sciences; Meninges - pathology; Meninges - ultrastructure; Metabolic diseases; Microscopy, Electron; Mucopolysaccharidoses - pathology; Mucopolysaccharidoses - surgery; Mucopolysaccharidoses - veterinary; Reference Values; Fissipedia; Brain; Animal model; Carnivora; Hurler syndrome; Biochemical analysis; Metabolic diseases; Cerebrospinal fluid; Genetic disease; Pathology; Vertebrata; Mammalia; L-Iduronidase; Treatment; Enzymatic activity; Surgery; Bone marrow; Glycosaminoglycan; Graft; Dog
• ISSN: 0031-3998; 1530-0447; 1530-0447
• DOI: 10.1203/00006450-198809000-00015

A naturally occurring disease in Plott hound dogs, caused by deficiency of the lysosomal enzyme alpha-L-iduronidase, was used to study the feasibility of bone marrow transplantation therapy in a neurodegenerative storage disease. Three long-term survivors of transplantation with littermate marrow at 5 months of age (before clinical signs) had CNS enzyme activity, glycosaminoglycan storage, and light microscopic and ultrastructural changes evaluated 594, 628, and 740 days after treatment. Iduronidase activity in small amounts (1-3% of donor values) was detectable in brain tissue. Cerebrospinal fluid had higher iduronidase activity after transplantation (7-15% of donor values). Enzyme activity within the CNS resulted in significant reductions in stored glycosaminoglycans and resolution, to a large extent, of light microscopic and ultrastructural lesions observed in affected, untreated littermate control dogs.