Zygogen is using its proprietary Z-Tag technology to develop novel, zebrafish-based model systems to enable drug discovery for neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Current neurodegenerative disease models have inherent limitations. Tissue culture assays and cell-based screens, such as cultures of spinal cord explants or isolated neurons, permit speed, throughput and assay of compounds but are limited by the lack of an organismal context. Current vertebrate animal models, such as mouse, rat and monkey, allow experimentation in a whole organism, but are expensive and are commonly used at later stages of the discovery process. Mammalian systems are not amenable to large scale screening of molecules or rapid transient knockout/knockdown genetic analysis. Models of neurodegenerative disease have been developed in invertebrates, such as Drosophila and C. elegans; however their nervous systems are less complex than that of the vertebrate zebrafish. Zebrafish models should provide rapid analysis of genes and compounds in a living vertebrate organism.
GPS expression driven by the neuron-specific portion of GATA-2 promoter is observed
in neurons of the brain and spinal chord (left panel) and in cell bodies and bodies of spinal chord motor neurons (middle panel). Embryos are 48 hours old, anterior to the left. Right panel, 6dpf larva with red fluorescent neurons (HuC promoter) in the brain. Arrows indicate the eye.