Human Developmental Neurotoxicity (DNT) Screening
RosetteArray platforms are engineered for high-throughput developmental neurotoxicity (DNT) screening. If you have chemical/drug candidates that you would like screened for human DNT risk, Neurosetta screen your compounds in-house using our standard forebrain and/or spinal cord assays. We will run 8-point dose-response studies to quantify your candidate’s impact on early human embryonic brain and spinal cord development (i.e., cell viability/cell proliferation, neural differentiation, and rosette/neural tube morphogenesis).
RosetteArray assays can detect disruptors of critical stages of human neurodevelopment not covered by other proposed assays (click image to enlarge).
Screening results will be provided as raw and graphed data with comparisons to RosetteArray data on known human developmental neurotoxins. Turnaround time for up to 10 compounds is ~2 months. Ultimate deceleration of risk assessment is dependent on the customers’ in vitro-to-in vivo extrapolation (IVIVE) and exposure level analyses (click image to enlarge).
Human Neurodevelopmental Disease (NDD) Modeling and Precision Medicine Discovery
RosetteArray technology can be used to model risk for a variety of neurodevelopmental disorders (e.g., neural tube defects, autism spectrum disorders, etc.).
Neural Tube Defect (NTD) Risk Assessment
Gene edited hPSC lines containing mutations associated with increased NTD-risk (MTHFRC677T) displayed increased sensitivity to folate metabolism inhibitor Methotrexate (MTX), and they were rescued with metabolized folic acid (5-MTHFA) supplementation. Neurosetta can assist in generating iPSC lines with your genetic background of interest and perform NTD risk assessment and drug discovery screens.
Click image to enlarge.
Lundin B.F. et al. RosetteArray Platform for Quantitative High-Throughput Screening of Human Neurodevelopmental Risk.bioRxiv[Preprint].2024 Apr https://doi.org/10.1101/2024.04.01.587605.
Autism Spectrum Disorder (ASD) Risk Assessment
RosetteArrays highlight morphogenesis differences between iPSCs derived from ASD patients with mutations in SYNGAP1, a gene encoding a neuronal synaptic protein. Patient-derived (ASDPatient) rosette tissues displayed impaired rosette formation efficiency compared to the gene edited ASDControl line. Neurosetta can develop a platform for your NDD model of choice, which can be translated to your benchtop or used for drug discovery screens at Neurosetta.
Click image to enlarge.
Birtele, M. et. al. Non-synaptic function of the autism spectrum disorder–associated gene SYNGAP1 in cortical neurogenesis. Nat. Neurosci. 26(2090-2103) (2023).
RosetteArray and Custom Micropatterned Well Plates
Neurosetta manufactures 96-, 24-, and 6-well RosetteArray plates for purchase. Also, we can manufacture micropatterned well plates with arrays of cell-adhesive features matching your geometries and dimensions of interest. All custom plates will be built using the same highly stable surface chemistry that makes RosetteArray plates capable of extended micropatterned culture.
Micropattern Examples
