Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing
Patent
1997-09-12
2000-03-14
Priebe, Scott D.
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
424 9321, 435325, A61K 4800, A61K 3500, C12N 1585
Patent
active
060369515
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention generally relates to cell transplantation and specifically to a method of transplanting cells which, following transplantation into the central nervous system (CNS), ameliorates the behavioral and functional deficits associated with neurological and neurodegenerative disorders.
BACKGROUND OF THE INVENTION
In treating disease it is often useful to treat tissue locally, rather than systemically, with trophic factors, particularly areas of tissue damage as for example in wound healing.
As a further example, transplantation of neural tissue into the mammalian central nervous system (CNS) is becoming an alternative treatment for neurological and neurodegenerative disorders including epilepsy, stroke, Huntington's diseases, head injury, spinal injury, pain, Parkinson's disease, myelin deficiencies, neuromuscular disorders, neurological pain, amyotrophic. lateral sclerosis, Alzheimer's disease, and affective disorders of the brain. Preclinical and clinical data indicate that transplanted cells (the graft) used in cell transplantation protocols for these types of neurodegenerative diseases survive and integrate with the host tissue, and provides functional recovery. (Sanberg et al., 1994).
The primary source for these grafts has been the fetus. For example, fetal ventral mesencephalic tissue has been demonstrated to be a viable graft source in Parkinson's disease. (Lindvall et al., 1990; Bjorklund, 1992). Likewise, fetal striatal tissue has been utilized successfully as graft material in Huntington's disease. (Isacson et al., 1986; Sanberg et al., 1994).
Neurologically dysfunctional animals have been transplanted with non-fetal cells and non-neuronal cells/tissue. For example, chromaffin cells from adult donors have been used in the treatment of Parkinson's disease. The major advantage of this type of transplantation protocol is that the graft source is not a fetal source and, thereby, circumvents the ethical and logistical problems associated with acquiring fetal tissue. Utilizing the chromaffin cell protocol, normalization of behavior is observed. However, the functional recovery of this behavior is temporary and the animals revert to their pre-transplantation status (Bjorklund and Stenevi, 1985; Lindvall et al., 1987). The inability of this type of treatment protocol to maintain normal behavioral activity in animals in the Parkinson's disease model renders clinical application of this protocol as well as other treatment therapies premature.
Administration of growth factors as a means of treating neurological and neurodegenerative diseases has been contemplated in the art. However, delivering these agents to the brain is fraught with great difficulties that have yet to be successfully overcome. Generally, these agents cannot be administered systemically and infusion into the brain is an impractical and imperfect solution. Engineering cells to deliver specific, single trophic factors when implanted in the brain has been suggested, but stable transfection and survival of the cells when implanted in the brain continues to be problematic. Additionally, it is becoming increasingly recognized that multiple trophic factors acting in concert are likely to be necessary for the successful treatment of neurological and neurodegenerative conditions.
Long term maintenance of functional recovery has been observed in a diabetic animal model utilizing a novel transplantation treatment protocol utilizing isolated islet cells and Sertoli cells. It is clear that the efficacy of the treatment is due to the presence of the Sertoli cells, in part, due to their known immunosuppressive secretory factor. (Selawry and Cameron, 1993; Cameron et al., 1990). Sertoli cells are also known to secrete a number of important trophic growth factors.
Accordingly, it would be desirable to utilize Sertoli cells alone as a source for diseases where growth and trophic factor support of damaged tissue is useful. Examples include, wound healing and neurological disorders including neurodegenerative disorders. The
REFERENCES:
Willing et al. (Nov. 1998) Mol. Med. Today, vol 4(11), 471-477.
Sanberg et al. (Dec. 1996) Nat. Biotech., vol. 14, 1692-1695.
Greenstein et al. (Mar. 1997) Nat. Biotech., vol. 15, 235-238.
Haque et al. (Apr. 1997) Mol. Med. Today, vol. 3 (4), 175-183.
Gao et al. (Apr. 1997) Exp. Opin. Ther. Pat., vol. 7 (4), 325-338.
M.D. Griswold (1992) The Sertoli Cell, Cacher River Press, Russel, L.D., and Griswold, M.D. eds., 195-200.
Bjorklunc and Stenevi, "Intracerebral neural grafting: a historical perspective" in Bjorklund, A and U. Stenevi, eds. Neural grafting in the mammalian CNS, Amsterdam: Elsevier, 3-11 (1985).
Bjorklund, "Dopaminergic transplants in experimental Parkinsonism: Cellular mechanisms of graft-induced functional recovery" Current Biology, 2:683-689 (1992).
Borlongan et al., "PR: Systemic 3-nitropropionic acid: Behavior deficits and striatal damage in rats" Brain Research Bulletin, 36:549-556 (1995).
Cameron et al., "Successful islet/abdominal testis transplantation does not require Leydig cells" Transplantation, 50:549-556 (1995).
Cameron and Muffly, "Hormonal regulation of spermatid binding to Sertoli cells in vitro." J. Cell Sci., 100:523-533 (1991).
Carson et al., "Synthesis and Secretion of a Novel Binding Protein for Retinol by a Cell Line Derived from Sertoli Cells "Journal of Biological Chemistry, 259:3117-3123 (1964).
Griswold, "Protein Secretion by Sertoli cells: general considerations" in Russell, L.d. and M.D. Griswold eds. The Sertoli Cell, Cache River Press, Clearwater, FL, 195-200 (1992).
Isacson et al., "Graft-induced behavioral recovery in an animal model of Huntington's disease" Proc. Natl. Acad. Sci., 83:2728-2732 (1986).
Koutouzis et al., "PR:Systematic 3-nitropropionic acid: Long term effects on locomotor behavior" Brain Research, 646:242-246 (1994).
Lindvall et al., "Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen" Ann. Neurol. 22:457-468 (1987).
Lindvall et al., "Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease" Science, 247:574-577 (1990).
Pakzaban et al., "Increased proportion of Ache-rich zones and improved morphological integration in host striatum of fetal grafts derived from the lateral but not the medial ganglionic eminence" Exp. Brain Res., 97:13-22 (1993).
Sanberg et al., "Cell transplantation for Huntington's disease" R.G. Landes Co., Boca Raton, FL, pp. 19-21 (1994). [n/a--will mail in].
Sanberg et al., "Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats" Nature Medicine, 3:1129-1132 (1997).
Selawry and Cameron, "Sertoli cell-enriched fractions in successful islet cell transplantation" Cell Transplant, 2:123-129 (1993).
Wictorin et al., "Reformation of long axon pathways in adult rat CNS by human forebrain neuroblasts" Nature, 347:556-558 (1990).
Borlongan Cesario V.
Cameron Don F.
Sanberg Paul R.
Beckerleg Anne Marie S.
Priebe Scott D.
University of South Florida
LandOfFree
Sertoli cells as neurorecovery inducing cells for neurodegenerat does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Sertoli cells as neurorecovery inducing cells for neurodegenerat, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sertoli cells as neurorecovery inducing cells for neurodegenerat will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-166411