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).

This technology includes multiple cells with various combinations of autophagy receptors knocked out. The cell lines include knockouts of the OPTN, NDP52, and TAX1BP1 genes that are involved in cargo selective autophagy. These lines may be used to explore how cell biology debris is catabolized, which may be relevant to neurodegenerative diseases like amyotrophic lateral sclerosis (ALS).

This technology includes the combination of an induced pluripotent stem cell (iPSC) line that can inducibly be differentiated into neurons (using an inducible Neurogenin 2, Ngn2, cassette) and enable CRISPR inhibition gene knockdown (via stable expression of dCas9-BFP-KRAB). The combination of these elements in a cell line enables multiple lines of research, including small molecule screens for drug development in neuronal disease models, as well as studying stem cell biology in an iPSC neuronal cell model.

This invention relates to the derivation of two stable cell lines, SVG5F4 and SVG1OB1, which can be used to study JC-virus infection. SVG cells are a heterogeneous population of immortalized human fetal glial cells, which express SV40 large T antigen. They are capable of supporting JC virus infection; however, the culture is mixed and changes over time. The two SV40-derived cell lines described here are stable over many passages.

This technology includes the creation and use of a polyclonal antibody for Neuroligin-4, NLGN4, that was created by injecting a peptide surrounding the pT707 phosphorylation site into rabbits and affinity purifying the resulting serum. Neuroligin-4 is a member of the neuroligin family of cell adhesion proteins. This family has been shown to play a role in the maturation and function of the neuronal synapse and has been implicated in patients with autism and intellectual disability.

The technology relates to the identification and validation of eight biomarkers for active central nervous system (CNS) intrathecal inflammation. The management of neuroimmunological diseases is severely hindered by an inability to reliably measure intrathecal inflammation. Current laboratory tests, that were developed over 40 years ago, do not capture low to moderate levels of CNS inflammation and provide limited information about its phenotype.

This technology includes an automated and non-invasive assessment system called Automated Identification of subjects at risks of Multiple Sclerosis (AIMS) to assist clinicians in their diagnostic evaluation. A focus of AIMS is the ‘central vein sign’ (and other radiological findings).

This technology includes a therapeutic approach to prevent secondary edema after cerebrovascular hemorrhage. Using an animal model, we found that edema is triggered by massive extravasation of myelomonocytic cells from the blood into the brain in response to hemorrhaging vessels. Administration of anti-LFA1 and anti-VLA4 antibodies resulted in an inhibition of extravasation of the myelomonocytic cells. This single dose treatment prevented secondary edema and markedly improved functional outcomes if administered within the first six hours following cerebrovascular hemorrhage.

This technology includes the identification and use of antisense oligonuclecotides (ASOs) complimentary to the 5’UTR of SMN2 (Survival of motor neuron 2) for the treatment of spinal muscular atrophy (SMA). SMA is an autosomal-recessive motor neuron disease caused by the loss of both copies of the SMN1 gene. Copies of the similar gene SMN2 decrease the severity of this disease in a dose-dependent manner. Thus, increasing expression levels of the SMN2 transcript can be used to treat SMA.

Cobalamin C deficiency (cblC) is the most common inborn error of intracellular cobalamin metabolism and is caused by mutations in MMACHC, a gene responsible for processing and trafficking dependent enzymes: intracellular cobalamin, resulting in elevated methylmalonic acid and homocysteine and methionine deficiency. Disease manifestations include growth failure, anemia, cardial defects and progressive blindness.