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Journal of
Nature and Science (JNSCI), Vol.1, No.1, e23, 2015 Neuroscience
Noninvasive intranasal stem
cells bypass the blood-brain barrier to target the brain to treat Parkinson's
disease, stroke, MS, brain tumors, cerebral ischemia, Alzheimer's and other CNS
disorders
William H. Frey II
Center for Memory & Aging (Alzheimer's Research Center),Regions Hospital, 640 Jackson
St., Together with my collaborators in Germany,
especially Lusine Danielyan M.D., we discovered and patented (1) that therapeutic
cells, including adult stem cells and genetically-engineered cells, can be
non-invasively delivered to the CNS using the noninvasive intranasal delivery
method that I developed (2). The first of our scientific papers on this new
discovery describes this successful method of delivery and proprietary
formulations that enhance delivery (3). The second of our papers
describes the successful treatment of Parkinson's disease in an animal model
with intranasal adult bone marrow derived mesenchymal stem cells (4). Intranasal stem cells bypass
the blood-brain barrier to target the brain by traveling extracellularly along the
olfactory neural pathway with minimal delivery to other organs. Once in the
brain, adult stem cells target the damaged areas of the brain specifically to
treat the underlying disease (4). Researchers at University Medical
Center Utrecht in the Researchers at Other researchers have reported
that intranasal stem cells target and treat brain tumors (11, 12). This
intranasal delivery, targeting and treatment technology can make stem cell
treatments practical for CNS disorders by eliminating the need for invasive
neurosurgical implantation of cells and by eliminating the need for intravenous
delivery that disperses cells throughout the body resulting in unwanted
systemic exposure. This delivery and treatment method can facilitate the
development of stem cell and genetically-engineered cell therapies for Parkinson’s,
PSP, Huntington's, Alzheimer’s, MS, epilepsy, stroke, neonatal ischemia, brain
tumors, traumatic brain injury (TBI), spinal cord (SCI) injury, etc. In humans, GnRH neurons or
Gonadotropin-releasing hormone expressing neurons are known to reach the brain
by using this same olfactory neural pathway during development. In
addition, pathologic cells, such as the amoeba Naegleria fowleri, are known to
enter the brains of humans by this same pathway and cause amoebic infection of
the brain. We have discovered how to use this pathway to delivery
therapeutic cells, including stem cells, to the brain to treat disorders of the
central nervous system. This intranasal therapeutic cell delivery,
targeting and treatment technology is available for licensing. References: 1. Frey, Danielyan and Gleiter (2012). Methods,
pharmaceutical compositions and articles of manufacture for administering
therapeutic cells to the animal central nervous system. U.S. Patent 8283160 B2
filed 2009 and issued October 9, 2012. 2. Frey,
W.H. 2nd (1997). Method of administering neurologic agents to the brain. US
Patent 5,624,898 filed 1989 and issued April 29, 1997. 3. Danielyan,
L., et al., Intranasal delivery of cells to the brain. Eur J Cell Biol, 2009.
88(6): p. 315-24. 4. Danielyan,
L., et al., Therapeutic efficacy of intranasally delivered mesenchymal stem
cells in a rat model of Parkinson disease. Rejuvenation Res, 2011. 14(1): p.
3-16. 5. van Velthoven, C. et al. Nasal administration
of stem cells: a promising novel route to treat neonatal ischemic brain damage.
Pediatr Res 2010. 68(5): p. 419-422. 6. Donega, V., et al., The endogenous
regenerative capacity of the damaged newborn brain: boosting neurogenesis with
mesenchymal stem cell treatment. J Cereb Blood Flow Metab, 2013. 33(5): p.
625-34. 6a. Kooijman, E., et al., Intranasal Mesenchymal stem
cell transplantation restores brain
damage, improves sensori-motor function and reverses depressive-like behavior
in a model of subarachnoidal hemorrhage in rats. Brain, Behavior, and Immunity.
2013, 32 (Supplement):e38. 7. Wei N., et al. Delayed intranasal delivery of
hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and
therapeutic benefits after ischemic stroke in mice. Cell Transplantation,
2013. 22(6) p. 977-991. 8. Fransson M., et al. CAR/FoxP3-engineered
T regulatory cells target the CNS and suppress EAE upon intranasal delivery. J
Neuroinflammation, 2012. 9:112. 9. Wu, S.,
et al., Intranasal Delivery of Neural Stem Cells: A CNS-specific, Non-invasive
Cell-based Therapy for Experimental Autoimmune Encephalomyelitis. J Clin Cell
Immunol, 2013. 4:310. 10. Fransson, M., et al., Intranasal delivery of
central nervous system-retargeted human mesenchymal stromal cells prolongs
treatment efficacy of Immunology, 2014. 142: p. 431–441.; 11. Reitz, M., et al. Intranasal delivery of neural stem/progenitor cells: A
noninvasive passage to target intracerebral glioma. Stem Cells Trans Med, 2012.
1(12): p. 866-73. 12. Balyasnikova, ___________ Correspondence
author: William
H. Frey II, Ph.D. Center for Memory &
Aging (Alzheimer's Professor of
Pharmaceutics, Neurology and Neuroscience Cell phone: 651-261-1998 ©
2015 by the Journal of Nature and Science (JNSCI) | www.jnsci.org |