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Decades of Research
Working together with collaborators in Germany, especially Lusine Danielyan, MD, we discovered (1) that therapeutic cells, including stem cells, immune cells (microglia, macrophages, etc.), and genetically engineered cells, can be delivered to the brain 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 in animals (3). The second of our papers describes the 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 specifically target the damaged areas of the brain, where they reduce neuroinflammation and treat the underlying disease (4).
Human Studies
Numerous researchers from around the world have published additional preclinical studies demonstrating the safety and efficacy of intranasal therapeutic cells in animal models of Parkinson’s, Alzheimer’s, brain tumors/glioblastoma, Huntington's, cerebral ischemia, stroke, traumatic brain injury, multiple sclerosis, and other disorders.
In humans, 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 deliver therapeutic cells to the brain to treat brain disorders (66).
In 2022, Baak et al (68) published a first-in-human study demonstrating that intranasal bone-marrow-derived MSC administration in neonates after perinatal arterial ischemic stroke is feasible with no serious adverse events observed in patients followed up to three months of age. This study follows a clinical observation paper reporting that the brain injury area of preterm infants with intracranial hemorrhage was significantly reduced following treatment with breast milk, including breast milk stem cells and nutritional factors (69). Most recently, researchers in China published a paper entitled Safety and Efficacy Outcomes after Intranasal Administration of Neural Stem Cells in Cerebral Palsy: a randomized controlled trial which reported that "Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment." (70). Additional clinical trials of intranasal stem cells for brain disorders are planned or in progress, and a detailed study protocol for a randomized controlled trial in ischemic stroke was recently published (71). A clinical trial in people with advanced Parkinson's showed not only safety but also preliminary efficacy with functional improvement in clinical outcomes with peak efficacy achieved at month six (72).
This intranasal delivery, targeting, and treatment technology can make therapeutic cell treatments practical for central nervous system disorders by eliminating the need for invasive neurosurgical implantation of cells and by avoiding intravenous delivery that disperses cells throughout the body, but mainly to the lungs, resulting in unwanted systemic exposure.
Additional details and references to the above information are available on request.