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Znomics Launches Obesity Drug-Discovery Program Based on OHSU Z-Fish Gene Model

Znomics this week launched a drug-discovery program designed to screen potential drug candidates using a proprietary genetic model of obesity in the zebrafish, a company official told CBA News.
The company licensed the obesity model from Oregon Health & Sciences University about a month ago and plans to further develop it so that it is applicable to drug discovery, said Stephane Berghmans, director of drug discovery at Znomics.
After identifying preclinical candidate compounds, the company will partner with a pharmaceutical or biotech company as a way to participate in clinical trials. Berghmans said that Znomics has not yet identified a partner.
The program spun out of work that was done in the OHSU lab of Roger Cone, a Znomics co-founder, said Berghmans. This work was published in two papers.
In the first paper, published in the December 2003 issue of the journal Endocrine, Cone and his team demonstrated that the melanocortin system regulated the metabolic state in the zebrafish.
In the second paper, published online in March 2007 in The Federation of American Societies for Experimental Biology journal, Cone and colleague Youngsup Song over-expressed in the zebrafish the agouti-related protein, a secreted hypothalamic factor regulated by metabolic state in mammals and involved in energy homeostasis. Cone and Song demonstrated that, just as in a rodent model, several different parameters, including weight, increase when AgRP is over-expressed.
Both papers established zebrafish on a physiological and biological level as a model system for the genetic analysis of energy homeostasis, said Berghmans.
“The advantage is that because you are dealing with the zebrafish larvae, they are very small, so you do not need a lot of compound, and you can also do it in a high-throughput fashion, if necessary,” he said.
Others in the field agree that zebrafish are an appropriate animal model for human diseases. “Many aspects of the zebrafish embryo are highly conserved between zebrafish and man,” said Nina Sawczuk, CEO and co-founder of Zygogen, a zebrafish company in Atlanta. “A lot of different therapeutic areas and disease states can be modeled [in zebrafish] and provide relevant data.”

“This obesity drug development program will not be our only drug development program.”

Peter Eimon, Zygogen’s director of research, said he thinks “there certainly is relevance for using the zebrafish as a model for obesity to the extent that people have been able to show that molecular pathways that play a role in appetite and metabolism are conserved and play the same function in zebrafish.”
However, modeling obesity in the zebrafish may be slightly more challenging than in other animal models, said Eimon. Other models of obesity, including rodent models, “typically cover a longer developmental timeframe, so they would be more challenging to do in zebrafish embryos or larvae,” which develop much more rapidly.
More People, More Space
Last November, Znomics announced that it had secured $4.9 million as part of a reverse merger with publicly traded shell company Pacific Syndicated Resources (see CBA News, 11/30/07). Znomics CFO Kerry Rea told CBA News at the time that the company planned to use the money to hire more employees and move to larger quarters so that it can add to its library of zebrafish strains.
The company is on track with its plans, said Berghmans, who was hired in March (see CBA News, 3/7/08) from UK drug discovery company Summit, which was formed after VASTox acquired DanioLabs (see CBA News, 3/23/07).
Berghmans said that he is currently interviewing to hire more personnel, and added the positions are scientific and primarily at the project-leader and technician level.
The number of new hires will depend on the therapeutic areas the company will focus on, which it is currently defining, said Berghmans. “I am working on several other drug-discovery programs for the company, as well as potential collaborations for assay development. This obesity drug-development program will not be our only drug-development program.”
He declined to elaborate.
Znomics moved to expanded facilities at OHSU at the end of February, in the university’s new Biomedical Research Building (see CBA News, 2/29/08).
Fish Market
According to Zygogen’s Sawczuk, biopharma is “still seeing the trends that we have been seeing for the last eight years, which is a steady increase in knowledge about zebrafish technology, and a validation and testing of the technology, essentially for drug discovery, primarily through compound screening.”
Zebrafish have two primary categories of use, disease modeling and toxicity testing, said Sawczuk. There are zebrafish assays that are essentially disease models or disease-like assays, on which people can screen compounds in various therapeutic areas, she said.
Another commercial application for zebrafish, toxicity testing, is “gaining momentum,” she added.

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