Fish to help in search for MS drugs

Study by the University of Bonn follows an innovative path in the search for new active substances

The zebrafish serves as a model organism for researchers around the world: it can be used to study important physiological processes that also take place in a similar form in the human body. It is therefore routinely used in the search for possible active substances against diseases. Researchers at the University of Bonn have now described an innovative way to do this. In this process, the larvae fish are made a bit more “human-like”. This humanization could make the search for active pharmaceutical substances much more efficient. The results of the pilot study have been published in the journal Cell Chemical Biology.

The zebrafish should be known to many aquarium enthusiasts mainly because of its striking pigmentation. However, the characteristic black-blue stripes, to which the animal owes its name, only form over time. Its eyelash-sized larvae, on the other hand, are still more or less transparent. Many developmental processes in their bodies can therefore be observed under the light microscope. For this reason, they now serve as a model organism for research groups around the globe.

“At the University of Bonn, for example, we are investigating how zebrafish repair defective nerve tissue,” explains Prof. Dr. Benjamin Odermatt from the Institute of Anatomy at the University Hospital Bonn. “We are also interested in this because many genes involved in this process also exist in a similar form in humans.” In principle, agents that boost these repair genes in fish could thus also work in humans. However, the differences between the genetic makeup of fish and humans are often significant. The larvae are therefore sometimes of limited use in the search for new drugs.

“We therefore took a different approach,” explains Prof. Dr. Evi Kostenis from the Institute of Pharmaceutical Biology at the University of Bonn. ” For a human gene known to play a role in the repair of nerve cells we looked for its counterpart in zebrafish. Then we excised this counterpart in the fish and replaced it with the human version.” The new genetic material took over the function of the original zebrafish gene. “If we now find a substance that boosts the repair processes in the fish with the human gene, there is a good chance that this will also be the case in humans,” says the scientist, who is also a member of the Transdisciplinary Research Area “Life and Health” at the University of Bonn. […]

Participating Core Facilities: The authors acknowledge the support from the Zebrafish Core Facility.

Participating institutions and funding:
The study was financially supported by the German Research Foundation (DFG).

Publication: F. Häberlein et. al.: Humanized zebrafish as a tractable tool for in vivo evaluation of pro-myelinating drugs; Cell Chemical Biology, DOI: 10.1016/j.chembiol.2022.08.007