T-cell therapy to neurodegenerative diseases
Provided is a method of treating a pathology associated with neural damage, the method comprising administering non-antigen specific polyclonal activated T cells and/or genetically modified T cells into the brain in a manner which prevents meningoencephalitis in the subject, thereby treating the pathology associated with neural damage. Also provided are devices for intrabrain and intrathecal administration of T cells, which comprise the brain-specific or non-antigen specific polyclonal activated T cells and/or genetically modified T cells and a catheter for intrabrain administration in a manner which prevents meningoencephalitis in a subject.
1. A method of treating Alzheimer's disease in a subject in need thereof, the method comprising:
(a) selecting non-cytotoxic CD4+ Abeta specific Th1 T cells from a pool of T cells,
(b) ex-vivo stimulating said non-cytotoxic CD4+ Abeta specific Th1T cells with an anti-CD3 and an anti-CD28 antibodies to thereby obtain activated non-cytotoxic Abeta specific CD4+ T cells that expresses interferon gamma, wherein said CD4+ T cells are autologous or allogeneic to the subject, and
(c) intracerebroventricularly administering an effective amount of said activated non-cytotoxic Abeta specific CD4+ T cells into the brain of said subject, wherein said administration results in (i) reduction in amyloid-beta plaques in the brain of the subject, and (ii) increase in neurogenesis in the granular area of the dentate gyrus (DG) in the brain of the subject, while preventing meningoencephalitis in the subject, thereby treating the Alzheimer's disease in the subject in need thereof.
2. The method of claim 1 , wherein said reduction in said amyloid beta plaques is of at least 30% as compared to administration of a control CD4+ T cells.
3. The method of claim 1 , wherein said activated non-cytotoxic CD4+ T cells accumulate in a hippocampus and cortex of the brain.
4. The method of claim 1 , wherein said intracerebroventricular administration is performed periodically.
5. The method of claim 1 , wherein said CD4+ T cells are autologous T cell of the subject.
6. The method of claim 1 , wherein said CD4+ T cells are allogeneic T cell.
7. The method of claim 1 , wherein the subject is a human subject.
8. The method of claim 1 , wherein said pool of T cells is comprised in a blood sample, a spleen sample or a lymph node sample.