Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1996-06-07
1998-08-11
Stanton, Brian R.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
424 931, 424 932, 424 9321, 424 937, 435 697, 435 701, 435 711, 4351723, 435325, 435368, 935 52, 935 70, 935 71, 935 99, 935102, C12N 1500, C12N 506
Patent
active
057929009
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to compositions useful for and methods of transplanting stable, homogeneous populations of neuron cells into non-human animals in order to generate non-human animal models useful to study human diseases, conditions and disorders. The present invention relates to compositions useful for and methods of transplanting stable, homogeneous populations of neuron cells into individuals in order to treat or prevent diseases, conditions and disorders, especially those characterized by loss, damage or dysfunction of the brain and/or loss, damage or dysfunction of an individuals neurons at other sites in the individual's body. This application is related to U.S. patent application Ser. No. 08/150,368 filed Nov. 9, 1993, U.S. patent application Ser. No. 08/170,668 filed Dec. 17, 1993, U.S. patent application Ser. No. 07/911,980 filed Jul. 10, 1992, and U.S. patent application Ser. No. 07/780,715, filed Oct. 21, 1991, now U.S. Pat. No. 5,175,103 issued Dec. 29, 1992, which are each incorporated herein by reference. This invention was made in the course of research sponsored by the NIH grant number NS18616. The United States Government has certain rights in this invention.
BACKGROUND OF THE INVENTION
The transplantation of major categories of central nervous system (CNS) cells (i.e. neurons, astrocytes) or CNS tissue fragments offers opportunities to study the developmental biology and immunological properties of these cells, to create animal models of CNS diseases such as Alzheimer's disease and to develop alternative strategies for the treatment of relentlessly progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and hereditary ataxia as well as to study other diseases, conditions and disorders characterized by loss, damage or dysfunction of neurons including transplantation of neuron cells into individuals to treat individuals suspected of suffering from such diseases, conditions and disorders. Indeed, recent pioneering efforts to utilize human fetal mesencephalic tissue grafts to ameliorate the extrapyramidal manifestations of drug induced and idiopathic Parkinson's disease emphasize the potential of transplanted human CNS tissues for the treatment of human neurodegenerative diseases (Freed, C. A., et al. 1992 New Engl. J. Med. 327:1549-1555; Spencer, D. D. et al. 1992 New Engl. J. Med. 327:1541-1548; and Widner, H., et al. 1992 New Engl. J. Med. 327:1556-1563) . However, the results of these efforts have not been completely satisfactory.
The immortalization of CNS progenitor cells using constructs containing temperature sensitive promoters has enabled transplantation of genetically engineered precursors of neurons and glia, but brain grafts of these progenitors have given rise to mixed populations of glial and neuronal progeny (Cattaneo, E., and R. McKay 1991 TINS 14:338-340; Renfranz, P. J., et al. 1991 Cell 66:713-729; Snyder, E. Y., et al. 1992 Cell 68:33-51). An alternative strategy has been to use neuron-like transformed cell lines obtained from tumors of the CNS, but neoplastic neuron-like cells usually cannot be induced to permanently exit the cell cycle or they develop into tumors when transplanted into the rodent brain (Fung, K.-F. et al. 1992 J. Histochem. Cytochem. 40:1319-1328; Trojanowski, J. Q., et al. 1992 Molec. Chem. Neuropathol. 17:121-135; and Wiestler, O. D. et al. 1992 Brain Pathol. 2:47-59). A slowly dividing human neuronal cell line obtained from a child with unilateral megalencephaly was shown to exhibit a neuron-like phenotype in culture but grafts of these cells in the rodent CNS showed a mixture of neuronal and mesenchymal phenotypic properties (Poltorak, M., et al. 1992 Cell Transplant I:3-15).
There is a need for a method of generating animal models of CNS diseases and disorders by transplanting neurons into the brains of such animals to produce conditions which resemble or mimic CNS diseases, conditions or disorders.
There is a need for animal
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Lee Virginia M.-Y.
Trojanowski John Q.
Stanton Brian R.
The Trustees of the University of Pennsylvania
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