Research Terms
Despite decades of investigations in both basic and clinic, the causes of Alzheimer’s disease (AD) and Parkinson’s disease (PD) still remain unknown. Current problem of developing therapies for these diseases is that many treatments are forcussing on symptomatic therapy and and never be successful showing any significant effect in clinical trials. Here we show that the drug therapies to increase neurogenesis and significantly improved behavior of mouse models, whcih could be a cure for AD and PD.
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Audience:
Adults
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1 hour or less
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Expenses Only
The University of Central Florida invention relates to the use of NANOG exosomal DNA as a diagnostic cancer marker. Specifically, the marker is a 22bp insert in the 3’UTR of the NANOG pseudogene, NANOGP8. Exosomes are extracellular microvesicles (30-100 nm) released by almost all types of cells upon fusion of the multi-vesicular body with the plasma membrane. Known for their role in cell-to-cell communication, exosomes have demonstrated an ability to unload their contents and contribute to the transformation of normal and stem cells to cancerous states.
University of Central Florida researchers have developed a xeno-free and transgene-free method for reprogramming mesenchymal stem cells to neural stem cell-like cells. Neural stem cells are difficult to obtain for therapeutic use due to their location in the brain. As an alternative, multipotent mesenchymal stem cells are a potential source of neural stem cells, but must first be reprogrammed into neural cells. Traditional cell reprogramming techniques often use transgenes which can be associated with tumorigenesis, limiting the clinical use of the reprogrammed cells.
Technical Details
This technology relates to a method for producing neural stem cell-like cells from adult mesenchymal stem cells without the use of animal products such as serum or gene transfection. The mesenchymal stem cells are treated with 1) decitabine (5-aza-2’-deoxycytidine) for modulating epigeneticity and 2) exosomes derived from neural stem cells for lineage specific signals. The resultant neural progenitors are capable of expanding and differentiating towards cells expressing neural markers.
Xeno- and transgene-free reprogramming of mesenchymal stem cells toward the cells expressing neural markers using exosome treatments, PLoS One. 2020 Oct 13;15(10):e0240469. doi: 10.1371/journal.pone.0240469.
Researchers at the University of Central Florida have developed an exosome-based approach for treating cancer and viral infections. The exosomes deliver gene-silencing molecules or protein inhibitors such as RNA interference (RNAi) or antibodies, respectively. Because exosomes are endogenous vesicles, this approach may limit immunogenicity and toxicity.
Technical Details
For anti-cancer treatment, the technology targets cancer stem cells which are a specialized subset of tumor cells that are often resistant to cancer therapy. The embryonic stem cell genes NANOG and OCT4 are expressed in cancer stem cells, but not in healthy adult cells. The exosomes deliver modulating agents that downregulate the expression of the embryonic stem cell genes NANOG or OCT4. As an example, targeting these genes by short hairpin RNA (shRNA) increased cell death in cancer stem cells treated with the chemotherapy drug Temozolomide in vitro.
For anti-viral treatment, the exosomes deliver knockdown agents that target the viral genome. As an example, a human lung fibroblast cell line was infected with human coronavirus 229E (HCoV-229E). The infected cell line was treated with exosomes containing shRNA that targeted HCoV-229E ORF4a which regulates viral production. Viral production was reduced in exosome/shRNA treated cells in vitro.
The University of Central Florida invention relates to a combination therapy to promote neuroregeneration consisting of 1) MS-818 to increase endogenous neural stem cells and 2) non-steroidal anti-inflammatory drugs to suppress inflammation.
A University of Central Florida researcher has developed a tissue image database system that enables users to search for and match images based on the presence of a target molecule, internal anatomical structure, or both. The patented system provides powerful tools that can help to expand and support medical and scientific research and informational exchange. For example, a user may be able to immediately determine whether a drug candidate affects a region or certain cells of the brain and from that information can predict its efficacy.
Current image databases employ mining tools that mainly use text-based ontologies and metadata. In contrast, the UCF invention can search the database using query images. The search engine may automatically extract visual characteristics of images presented as queries, search image databases, and list candidate images with characteristics similar to the original queries. This system can perform reverse searches, namely mining data associated with the image using visual features between the query and original image.
Technical Details
The UCF invention comprises a user-accessible tissue image database system and methods for using it. An example system setup can include a computer unit with at least one processing module, at least two computer-readable program code modules, and multiple digital images of tissue samples indicating a target molecule. It may also take the form of hardware or a combination of software and hardware with a storage medium, such as hard disks, CD-ROMs, DVDs, optical storage devices or magnetic storage devices. The system can include images of internal tissue obtained by magnetic resonance imaging or X-ray in PGM format.
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.
Stage of Development
Prototype in development.
Researchers at the University of Central Florida have developed a technology for camera-based fingertip tracking that is less expensive and less complicated than existing methods. The technology enables users to input information into a computer without using conventional mechanisms such as a keyboard, pointing device, mouse, trackpad or touch-sensing displays. Unlike other fingertip tracking methods that require a flat surface or expensive, complicated combinations of infrared lasers and steering mirrors, the UCF invention can track movement in free space using ordinary cameras.
Technical Details
The UCF invention comprises a system and methods for determining user input from a series of movements captured in video frames. A system can include a video camera configured to produce a series of video frames, memory configured to store program code, and a processor that can provide user input to an application. In one example implementation, the video camera captures fingertip motions in a series of video frames. The system’s software analyzes the video frames to identify fingertip locations and movement. The software then maps each fingertip location relative to a virtual user input device and provides the input to the application.
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.
Stage of Development
Prototype available.
Researchers at the University of Central Florida are developing a topical treatment to promote hair growth. The active compound is a heterocyclic pyrimidine known as NBI-18. The researchers previously found that NBI-18 stimulated the proliferation of neural stem cells. They hypothesized that NBI-18 could restore hair growth by increasing cell proliferation of endogenous stem cells within the hair follicle. They found that topical application of NBI-18 induced visible hair regrowth on treated areas in shaved mice. Toxicity studies suggested no adverse effects on the mice.
Technical Details
This technology is a treatment for promoting hair growth by topical application of the compound NBI-18. To test for hair regrowth, the researchers shaved mice at four specific lateral/dorsal regions in a circular pattern. NBI-18 was suspended in 50% ethanol (ETOH) at concentrations of 0.75, 1.5, and 3.0 mg/ml and applied to the shaved areas for five consecutive days. On days four and five, Bromodeoxyuridine (BrdU) (100 mg/kg) was intraperitoneal injected (i.p.) to detect cell proliferation. NBI-18 treatment resulted in predominant hair regrowth on the treated areas with a similar growth to the original length within seven days. Immunohistochemistry showed an increase in BrdU positive cells in all NBI-18 treated regions compared to ETOH controls.
To test for acute toxicity, NBI-18 was injected for seven days at 0, 100, 300, and 1000 mg/kg/day (i.p.). Behavioral testing was performed with rotarod and open field tests to examine the balance and coordination of the mice before, during, and after NBI-18 injection. Additionally, postural reflex and forelimb placing tests were performed to evaluate neurological functions. The postmortem brains were also processed for immunohistochemistry. The animals demonstrated no immediate behavioral or neurological changes and no symptoms of toxicity from NBI-18 throughout the studies.
Also, a third-party laboratory performed an Ames test, and the results suggested no mutagenesis or toxicity.
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.
Stage of Development
The compounds have been tested in mice.
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 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 details about the combination therapy and the structure of NBI-18, refer to the issued patent: US 10751340 B2
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.