Endogenous Stem Cell-Based Therapy for Neurodegenerative Diseases

  • Stem cell-based treatment for neurodegenerative conditions in which there is a loss of neurons
  • Combination treatment of Posiphen ((+)-phenserine) and NBI-18
  • Co-treatment increased neural stem cell production and improved memory function in an Alzheimer’s disease mouse model

Abstract
The University of Central Florida invention is a stem cell-based therapy for the treatment of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. While stem cell transplantations have been explored as treatments for neurodegenerative diseases, the ability of the implanted cells to properly localize and differentiate is a clinical challenge. An endogenous stem cell-based therapy may be a promising new approach for treating neurodegenerative diseases.

This invention comprises the co-administration of the compounds Posiphen ((+)-phenserine) and NBI-18 to promote neurogenesis. Posiphen is known to reduce the synthesis of the amyloid precursor protein. NBI-18, a compound that crosses the blood-brain barrier in mouse models, increases endogenous neural stem cells in the mouse brain. By using both compounds, UCF researchers found that NBI-18 increased stem cell proliferation and that the effect was maxed at 3 mg/kg. There was a correlation between cell count and behavioral data; animals that showed improvement in cognition had more neurons in their brains.

Technical Details

The UCF technology is a combination treatment for improving brain function and/or promoting neurogenesis in a patient suffering from a neurodegenerative condition.

UCF researchers previously found that high concentrations of the amyloid precursor protein cause glial differentiation of neural stem cells by activating inflammatory cytokine signaling. This effect limited the efficacy of NBI-18 for regenerating neurons when administered alone. The combination treatment of NBI-18 and Posiphen increased neural stem cell production and improved memory function in Alzheimer’s disease mouse models (5xFAD mice). Memory function was tested by a radial water maze test. Neural stem cell production was analyzed by immunohistochemistry of the postmortem brain.

For behavioral and memory testing, the mice were trained in a radial water maze during a pre-treatment period. After the mice had reached the criterion for the pre-treatment behavioral testing, they were injected with Posiphen (25 mg/kg) (s.c.) once a day for seven consecutive days; followed by a combination of Posiphen (25 mg/kg) and NBI-18 (0, 3, 10 mg/kg) which was injected (s.c.) once a day for seven consecutive days; followed by another series of Posiphen (25 mg/kg) injections (s.c.) once a day for seven consecutive days. On the final two days of the combination injections, an injection of BrdU (100 mg/kg) was administered separately (s.c.) once per day.

After the treatment regimen, the animals were tested again in the radial water maze. Combination treatment of Posiphen and NBI-18 (3 mg/kg or 10 mg/kg) improved the memory of the 5xFAD mice, and they behaved similarly to the wild-type mice in the radial water maze. As noted, animals that showed improvement in cognition had more neurons in their brains. NBI-18 toxicity has been tested up to 1000 mg/kg in mice. No kidney or liver toxicity has been detected.

For more information, refer to the following:

Technology 34026 is a drug therapy method for co-administering Posiphen and NBI-18 to a patient. For more details about the combination therapy and the structure of NBI-18, refer to US Patent 10,751,340 B2.
Technology 34533 is a drug treatment method of co-administering phenserine and a stem cell proliferating pyrimidine compound (SCPPC). For more details, refer to the published patent application: US20210046079A1.
Partnering Opportunity

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