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Many experimental therapies will rely on the local parenchymal delivery of macromolecules or nucleic acids for their success. However, the volume of distribution of many of these potential therapeutic agents is restricted by their interactions with the extracellular matrix and cellular receptors.

The vanilloid receptor (VR) is a cation channel predominantly expressed on the peripheral processes and perikarya of nociceptive primary afferent neurons. Previous studies have shown that activation of the peripheral receptors by agonists such as capsaicin from hot peppers, or the much more potent resiniferatoxin, produces acute pain sensation which may be followed by desensitization. These inventors discovered that administration of VR agonists in the vicinity of neuronal cell bodies expressing the VR receptor can actually destroy those cells.

This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF).

This technology includes the identification and use of 12/15-lipoxygenase (LOX) inhibitors, including ML351 and related analogs, for post-stroke treatment. The 12/15-LOX directly oxidizes lipid membranes leading to their direct attack. After a stroke, the activity of 12/15-LOX is upregulated and is thought to contribute to increased neuronal loss and blood-brain barrier leakage. A high-throughput screen was undertaken to find inhibitors, which were then subjected to medical chemistry optimization.