The InDanio screening system can be used, for example, to functionally characterize ‘orphan’ receptors – those for which their natural ligands or specific function are unknown – and thus qualify them as potential targets for drug discovery. The system can also be used to screen compound libraries in order to identify and refine potential new drugs that target NR proteins.
NRs are found inside cells and are responsible for sensing the presence of hormones and other molecules. They regulate the expression in the cell of a number of genes involved in homeostatic, metabolic and reproductive processes.
NRs regulate the expression in the cell of a number of processes, and they also represent an important and successful class of drug targets implicated in some of the most prevalent diseases, including immune disorders, obesity, diabetes and cancer.
A study four years ago determined that one seventh of drugs approved by the U.S. Food and Drug Administration (FDA) target nuclear receptors, and the top ten selling NR-based drugs combined represent worldwide annual sales of over USD $16 billion.
Although many NRs have been targeted successfully, most of them have not been, and one third of them are still orphans.
InDanio was founded by Dr. Henry Krause, a professor in the Banting and Best Department of Medical Research at the University of Toronto, and Dr. Jens Tiefenbach, a post-doctoral fellow working with Dr. Krause and is based on the IP portfolio generated by their research.
“The OGI investment will allow InDanio to characterize the function of ill-understood members of the NR family and thus form the basis for establishing commercial partnerships to further characterize such receptors and develop drugs targeting them,” commented Dr. Paul Chipperton, member of the InDanio board of directors and CEO of Profound Medical.
“With a more efficient and comprehensive approach to probing the NR receptors, there is a tremendous opportunity to develop new therapeutic avenues into the NR family.”
InDanio’s zebrafish ligand trap (LT) technology and LT drug discovery platform will take advantage of the fact that zebrafish are transparent in early stages of development, thus allowing for the use of fluorescent protein markers. Many drugs never reach the marketplace because they fail toxicology tests or have other unintended effects on the body.
Currently, in vitro testing relies on measuring simple chemical interactions to gauge a drug’s effectiveness, but this is often not an effective predictor of how drugs will affect living organisms.
By beginning the screening process with in vivo assays using live zebrafish, more information on a drug’s effectiveness, toxicology and other side-effects can be gathered in advance of and to better inform downstream clinical trials.
“InDanio is in an excellent position to capitalize on the significant work undertaken by the academic and pharma sectors over the past 20 years in characterizing NR proteins and developing compound libraries targeting these proteins,” commented Dr. Christian Burks, President and CEO of OGI.
“Their screening system should provide novel, productive information on natural ligands, tissue and developmental specificity of natural or xenobiotic compounds, and whether or not a compound binds multiple receptors.”
Source: Alastair Harris-Cartwright
Ontario Genomics Institute