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This technology includes A1AR-selective agonists which are full or partial agonists of the A1AR and are being considered for treatment of various conditions: seizures, stroke, diabetes, pain, cardio-protection and arrhythmias. A1AR agonists are highly neuroprotective in ischemic and epileptic models. A1AR agonists are also being explored for antidepressant, antianxiety, and other neuropsychiatric effects, due to their presynaptic action to decrease the release of excitatory amino acids in the brain.

This technology includes a cell line to be used for the study of anti-psychotic therapies and potentially Parkinson’s disease. Activation of D1 dopamine receptors plays a critical role in many fundamental CNS processes. M4 mAChRs are coexpressed with D1 dopamine receptors in a specific subset of striatal medium spiny neurons that contain GABA as the major neurotransmitter. The present study used Cre/LoxP technology to generate mutant mice that lack M4-¬-AChRs only in D1 dopamine receptor-¬-expressing cells to investigate the physiological relevance of mAChRs in this neuronal subpopulation.

This technology includes (N)-methanocarba derivatives that are selective agonists of the A3 receptor to be used for the treatment of chronic neuropathic pain. This class of compounds produced full agonists of the human A3AR of nanomolar affinity that were consistently highly selective (>1000-fold vs. A1AR and A2AAR). The selectivity at mouse A3 receptors is smaller, but the compounds are still effective in vivo in reducing or preventing development of neuropathic pain.

This technology includes new nucleoside inhibitors containing rigid rings that provide high potency for use as antiepileptic drugs. Adenosine kinase (AdK) inhibitors raise the level of endogenous adenosine, particularly in disease states, and are of interest for the potential treatment of seizures and neurodegenerative and inflammatory conditions.

This technology includes lentivirus vectors to be used to treat sickle cell disease and beta thalassemia. (i) Lin28A or Lin28B vectors designed for erythroid-specific expression using EKLF1, SPTA1, or similar erythroid-specific regulatory elements will be used to transduce hematopoietic stem cells isolated from humans with sickle cell disease or beta-thalassemia syndromes.

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.

This technology includes MRS4322, which is an A3 agonist that is currently being evaluated for treatment of traumatic brain injury. Although its affinity in the receptor is in the micromolar range, it enters the brain in sufficient concentration to activate a protective CNS receptor, A3 adenosine receptor. Potential applications of such A3 agonists could also include neurodegenerative conditions.

Scientists at the NIH disclosed a novel adeno-associated virus (AAV) termed "44-9." AAV44-9 based vectors have high gene transfer activity in a number of cell types, including salivary gland cells, liver cells, and different types of neurons (e.g., cells of the cortex, olfactory bulb, and brain stem, and Purkinje cells of the cerebellum). These vectors can increase the transduction efficiency and decrease the potential of being neutralized by preexisting antibodies compared to the wild type AAV.