Batten's disease: failure of allogeneic bone marrow transplantation to arrest disease progression in a canine model

We investigated whether the course of canine ceroid lipofuscinosis (CCL), a model of Batten's disease in man, was affected by allogeneic bone marrow transplantation. Four English setters with CCL, 4 months of age, were given 9.2 Gy of total body irradiation, followed by the infusion of bone marrow cells from healthy DLA identical sibling donors. All transplanted dogs had complete hematologic reconstitution. However, at 12–13 months posttransplant, all dogs developed characteristic and progressive signs of CCL. Autopsies revealed cerebral atrophy and findings of ceroid storage not different from those in non‐transplanted controls. These findings suggest that bone marrow cells do not contain or release the gene product(s) necessary to correct the disease. It appears unlikely that with our current knowledge, allogeneic marrow transplantation would be beneficial in the treatment of Batten's disease.

[1]  G. Constantopoulos,et al.  Long-term effects of bone marrow transplantation in dogs with mucopolysaccharidosis I. , 1989, The American journal of pathology.

[2]  R. Storb,et al.  Allogeneic bone marrow transplantation for canine ceroid lipofuscinosis. , 1989, Transplantation Proceedings.

[3]  G. Wagemaker,et al.  Effect of bone marrow transplantation on enzyme levels and clinical course in the neurologically affected twitcher mouse. , 1988, The Journal of clinical investigation.

[4]  N. Koppang.  The English setter with ceroid-lipofuscinosis: a suitable model for the juvenile type of ceroid-lipofuscinosis in humans. , 1988, American journal of medical genetics. Supplement.

[5]  W. Krivit,et al.  Bone marrow transplantation for genetic diseases. , 1987, The New England journal of medicine.

[6]  H. Deeg,et al.  JOINT REPORT OF THE THIRD INTERNATIONAL WORKSHOP ON CANINE IMMUNOGENETICS: II. ANALYSIS OF THE SEROLOGICAL TYPING OF CELLS , 1987, Transplantation.

[7]  N. Koppang.  Hereditary ceroid lipofuscinosis in English setter dogs: a model for human neuronal ceroid-lipofuscinosis and aging , 1987 .

[8]  G. J. Stewart,et al.  Correction of enzyme deficiency by allogeneic bone marrow transplantation following total lymphoid irradiation in dogs with lysosomal storage disease (fucosidosis). , 1986, Transplantation proceedings.

[9]  N. Bazan,et al.  Change in content, incorporation and lipoxygenation of docosahexaenoic acid in retina and retinal pigment epithelium in canine ceroid lipofuscinosis , 1985, Neuroscience Letters.

[10]  I. Mayhew,et al.  CEROID‐LIPOFUSCINOSIS (BATTEN'S DISEASE): PATHOGENESIS OF BLINDNESS IN THE OVINE MODEL , 1985, Neuropathology and applied neurobiology.

[11]  R. Dinsmore,et al.  Marrow transplantation for congenital disorders. , 1984, Seminars in hematology.

[12]  G. Fishman.  Ceroid-lipofuscinosis (Batten's Disease) , 1984 .

[13]  H. Deeg,et al.  COMBINED IMMUNOSUPPRESSION WITH CYCLOSPORINE AND METHOTREXATE IN DOGS GIVEN BONE MARROW GRAFTS FROM DLA‐HAPLOIDENTICAL LITTERMATES , 1984, Transplantation.

[14]  R. Nuscher,et al.  Bone marrow transplantation. , 1977, The American journal of nursing.

[15]  H. Braak,et al.  Canine ceroid lipofuscinosis, a model for ageing of the human isocortex. , 1984, Gerontology.

[16]  H. Deeg,et al.  The canine major histocompatibility complex. Population study of DLA-D alleles using a panel of homozygous typing cells. , 2008, Tissue antigens.

[17]  J. Clausen,et al.  Leucocyte glutathione peroxidase activity and selenium level in Batten's disease. , 1983, Scandinavian journal of clinical and laboratory investigation.

[18]  H. Goebel,et al.  Ultrastructure and visceral distribution of lipopigments in infantile neuronal ceroid-lipofuscinosis. , 1982, Pathology, research and practice.

[19]  G. Sale,et al.  The ultrastructure of the human epidermis in chronic graft-versus-host disease. , 1979, The American journal of pathology.

[20]  R. Storb,et al.  MARROW GRAFTS BETWEEN DL‐A‐MATCHED CANINE LITTERMATES , 1973, Transplantation.

[21]  N. Koppang.  Canine ceroid-lipofuscinosis-a model for human neuronal ceroid-lipofuscinosis and aging. , 1973, Mechanisms of ageing and development.

[22]  N. Koppang.  Neuronal Ceroid-Lipofuscinosis in English Setters Juvenile Amaurotic Familiar Idiocy (AFI) in English Setters* , 1969 .