http://www.jnsci.org/index.php?journal=nsci&page=article&op=view&path[]=23&path[]=98
William H. Frey II
Center for Memory & Aging (Alzheimer's Research
Center), Regions Hospital, 640 Jackson St., St. Paul, MN 55101, Department of Pharmaceutics, Neurology and
Neuroscience,
University of Minnesota, USA.
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 Netherlands have demonstrated the
effectiveness of intranasal stem cell treatment technology in an animal model
of neonatal cerebral ischemia (5) and also in animals with neonatal brain
damage (6) and subarachnoid hemorrhage (6a).
Researchers at Emory University
have used our intranasal stem cell treatment successfully in an animal model of
stroke (7), and researchers at Uppsala
University in Sweden have
demonstrated that intranasal T regulatory cell therapy delivered and targeted
the cells to the brain and efficiently suppressed ongoing inflammation in an
EAE model of multiple sclerosis leading to reduced disease symptoms (8).
Intranasal adult neural stem cells have also been shown to improve the
EAE model of MS (9) as have intranasal mesenchymal stromal cells (10).
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.
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