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This technology includes a method for creating functional, brain region-specific neural spheroids that can be used for disease modeling and therapeutic testing of compounds for neurological diseases. The developed protocol uses somatic cells, including iPSC-derived neurons, as well as astrocytes using means such as 96- or 384-well ultra-low attachment round-bottom plates. Spheroids have been generated using this method that model brain regions such as the ventral tegmental area and prefrontal cortex, which are implicated in Parkinson’s and Alzheimer’s disease.

This technology includes two new salt forms for (2R,6R)-hydroxynorketamine (2R,6R-HNK), which is the lead molecule being developed for treatment-resistant depression. Currently, 2R,6R-HNK is being developed as the HCl salt. The HCl salt is slightly hygroscopic at high RH. This is a potential liability, especially in an oral pill form. Recently the malonate and salicylate salt have been discovered and found to have excellent crystalline behavior while also not having the hygroscopic liability the HCl salt holds. This represents a clear advantage.

In the last decade, prescription opioid abuse and misuse has been a major contributor to mortality in the United States, resulting in a serious national public health crisis. Nearly 12 million Americans used prescription opioids nonmedically in 2018, with >67,000 people dying from an opioid overdose.

This technology includes the identification and use of a ketamine metabolite, (2R,6R)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone (HNK), for the treatment of depression. Ketamine is an NMDA receptor antagonist that exerts a rapid and sustained antidepressant and anti-suicidal effect. However, even low doses of ketamine has addictive and psychomimetic effects. The downstream metabolite, (2R,6R)-HNK, does not inhibit the NMDA receptor but recapitulates the antidepressant and anti-suicidal effect of ketamine.

This technology includes a transgenic mouse model of Niemann-Pick Disease Type C (NPC), which is a rare neurodegenerative disorder, characterized by intracellular accumulation of cholesterol and gangliosides. The mouse strain, Tg(Npcl), expresses wild-type NPC1 gene under the control of the prion promoter. When combined with the NPC deficient mouse model, BALB/c npcnih/nih, also known as Npcl-/-, the transgene insertion allele rescues life expectancy of Npc1-/- mice. Npc1-/- mouse have reduced life expectancy and die around 8 weeks, making it a difficult model to be utilized.

This technology includes a group of radioligands that label inflammatory cells specifically, accurately, and across different genotypes and can be detected using Positron Emission Tomography (PET). The radioligands target the Translocator protein 18 kDa (TSPO) receptor which is present on the outer mitochondrial membrane and is involved in the production of steroids. Current TSPO radioligands either lack specificity or have highly variable inter-subject sensitivities due to TSPO genotypic differences.

This technology includes a group of radioligands that label inflammatory cells specifically, accurately, and across different genotypes and can be detected using Positron Emission Tomography (PET). The radioligands target the Translocator protein 18 kDa (TSPO) receptor which is present on the outer mitochondrial membrane and is involved in the production of steroids. Current TSPO radioligands either lack specificity or have highly variable inter-subject sensitivities due to TSPO genotypic differences.

The invention is a panel of five tests of patient sera for immune responses that may attack the brain and lead to the characteristic symptoms of pediatric acute neurologic syndrome (PANS). PANS is a condition defined by a sudden onset of obsessive-compulsive symptoms, eating restrictions, and other cognitive and/or behavioral symptoms. Currently, the diagnosis of PANS is made when other possible symptoms are ruled out, a diagnosis of exclusion.

This invention includes the design and synthesis of ligands that bind selectively and specifically to the NR2B subunit of the NMDA receptor. The NMDA receptor is thought to play a role in the pathophysiology of psychiatric disorders, including depression, stroke, drug addiction, and neuropathic pain. Existing ligands to the NMDA receptor are widely used to treat these conditions.

This technology relates to a closed-loop controller that is being developed as a phone app for emotional self-regulation in real-time. There is a significant association between emotion dysregulation and symptoms of depression, anxiety, eating pathology, and substance abuse, affecting millions worldwide. Consisting of a closed-loop controller that adjusts reward values in real-time according to individual mood response, the Mood Machine Interface technology compensates for adaptation to stimuli over time allowing it to generate substantial mood changes in the user.