Johns Hopkins team uses zebrafish to develop a new drug screening tech


High throughput screening was once viewed as the very salvation of the drug development world. The automated system developed in the '80s could test hundreds of potential drugs in robotic fashion, looking for the telltale "hits" that could flag a possible new therapy. The problem, though, was that the effects they were seeing with HTS screening rarely translated in more complex animal models--or stood a chance in humans.

Now a group of research scientists at Johns Hopkins say they developed a new approach that relies on embryos from genetically modified zebrafish to replace cell and tissue samples used in HTS. And they say that the new approach could signal a revolution in translational research with a new, better and much more efficient technology.

To test it, the researchers bred zebrafish--a commonly used lab animal--in which insulin-generating beta cells would glow yellow against a background of red for all other cells. And they took 500,000 zebrafish embryos to use in the tiny wells used in HTS, testing a variety of existing diabetes drugs as well as many others.

In the end, they came up with 24 possible new diabetes drugs that clearly increased the number of beta cells in the process. In some cases, they also stumbled across new pathways that may be involved in diabetes, including the serotonin pathway involved in brain signaling. And the same technique could be replicated in other diseases.

"More studies need to be done, but we think there's potentially no limit on the diseases this screening technique could be applied to other than the human imagination," says Jeffrey Mumm, Ph.D., associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute and McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine.

Their work is described in the August 14th issue of eLife.

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