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This invention relates to the stable and high-yield production of a high-potency toxin protein called DT390-EGF. This toxin was developed for the treatment of EGF-receptor-positive cancers, including bladder cancer. Initial methods for synthesizing DT390-EGF relied on the use of E. coli. However, the production in E. coli was difficult to prepare and had limited stability. Repeated efforts to standardize the process in E. coli gave poor yields, purity, and high variation.

This technology includes the generation and use of an antibody that can detect endogenous Neuroligin 4Y, NLGN4Y, a cell adhesion molecule on the X-chromosome. NLGN4Y is part of an X-Y pair with NLGN4X, which has been implicated with autism spectrum disorder (ASD) and intellectual disability. ASD has a sex bias etiology that is not well understood, affecting four times as many males as females. Previous work has revealed a potential pathogenic mechanism for male-bias based on mutations in NLGN4X and NLGN4Y. The use of the NLGN4Y antibody could be used to study potential mechanisms.

This technology relates to the therapeutic use of antibodies to decrease the potential neurodegenerative effect of the HERV-K retrovirus. Previous work has shown that patients with Amyotrophic Lateral Sclerosis (ALS) can have HERV-K activation. In animal models, activation of HERV-K can lead to neurodegenerative symptoms similar to those exhibited by ALS patients. This neurodegenerative effect is thought to be caused by the release of HERV-K envelope proteins into the extracellular space. Work with monoclonal antibodies in vitro has neutralized the toxicity of this protein.

This invention includes human induced pluripotent stem cell (iPSC) lines that harbor a single copy dCas9-BFP-KRAB at the CLYBL safe harbor locus (mediating CRISPR inhibition of human gene expression) and/or a single copy of dox-inducible NGN2 at the AAVS1 locus (enabling the differentiation of the iPSCs into neurons). The CRISPR-mediated inhibition of human gene expression is maintained into the differentiated neurons, permitting functional studies of targeted genes in neurons.

This technology relates to the creation and use of newly identified ligands to the D1 dopamine receptor (D1R). The D1 dopamine receptor is linked to a variety of neuropsychiatric disorders and represents an attractive drug target for the enhancement of cognition in schizophrenia, Alzheimer disease, and other disorders. These ligands are positive allosteric modulators (PAMs) that bind to the dopamine receptor at a site other than where dopamine binds and causes the receptor to have an increased response.

The technology relates to therapeutic approaches that inhibit and block the replication of the endogenous HERV-K retrovirus. Previous work has shown that patients with Amyotrophic Lateral Sclerosis (ALS) can have HERV-K activation. In animal models, activation of HERV-K can lead to neurodegenerative symptoms similar to those exhibited by ALS patients. Work in these animal models has allowed the identification of the responsible transcription factor (TDP-43) as well as the corresponding positions of the HERV-K promoter binding sites.

The technology includes USP30 knockout HeLa cells that were generated using CRISPR technology. Parkin and Pink1 are key master genes for triggering the degradation of mitochondria (mitophagy). In contrast, USP30 has been found to be localized in the mitochondria and have a role in antagonizing Parkin function, thereby impeding mitophagy.

This technology involves the generation and use of a mouse model for studying hypogonadism in humans and a cell line to study cellular and molecular properties of gonadotropin-releasing hormone (GnRH) cells. The mouse model expresses the simian virus 40 T antigen driven by the GnRH promoter, resulting in hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway. Olfactory bulb tumors in this model animal were dispersed, and GnRH-secreting neuronal cell line (GN/NLT cell line) was established.

This invention relates to the synthesis and methods of using a drug, deuterated L-DOPS, to treat deficiencies in the neurotransmitter norepinephrine. This classic neurotransmitter has roles in both the brain and the periphery. In the brain, norepinephrine is thought to play important roles in attention, memory, sleep, pain, movement, distress, and mood. Outside the brain, norepinephrine mediates regulation of the circulation by the sympathetic nervous system by increasing blood pressure.

This technology includes the generation and use of HeLa cell lines that have the TANK-binding kinase 1 (TBK1) gene knocked out solely or in combination with either the genes NDP52 or OPTN. Both NDP52 and OPTN are receptors involved in the degradation of mitochondria, mitophagy. The TBK1 kinase has a role in enhancing the effect of mitophagy on these receptors. Mutations in TBK1 have been shown to be associated with neurodegenerative diseases such as Parkinson, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).