Researchers worldwide are driven by the search for new antibiotics or virostatics that keep multidrug-resistant pathogens at bay or fight new pathogens. If an active ingredient looks promising, it has to be put through its paces before it can be approved for use in humans and animals. This process starts in the test tube, but at some point research on living organisms becomes unavoidable to prevent undesirable side effects in humans.
Zebrafish larvae could become the game-changer in drug and toxicity testing. "The special thing about these larvae is that they already develop an organ system with kidneys and liver in the first 120 hours after fertilization. Whether an active substance can be degraded by the organism or shows toxic side effects can therefore be tested much better on them than on simple cell culture models," says Dr Jennifer Herrmann, team leader for biology at HIPS. HIPS is a site of the Helmholtz Centre for Infection Research in collaboration with Saarland University.
Because of their good comparability with more highly developed species, larval experiments can partially replace animal experiments in the early preclinical development of drugs. At HIPS, larvae are already successfully used on a small scale in drug discovery. For this, the institute's zebrafish team was awarded the research prize "Alternatives to Animal Testing" by the Saarland Ministry of the Environment last summer.
The problem: So far, the method can only be used for a limited number of tests. This is because each larva still has to be examined twice a day under the microscope by a researcher. Changes in larval development that occur as a result of treatment with drug candidates are often difficult to detect with the naked eye. If pathological changes or influences on the development of the larvae occur, the rapid development of the larvae makes it difficult to determine exactly when they occurred. The method is also very time-consuming and therefore not yet applicable on a large scale.
Together, HIPS and CISPA want to change that. "We will develop image-based machine learning methods that can predict larval development at a very early stage after testing, and detect anomalies. Thus, many test series can be terminated ahead of time, saving time and money. It also allows us to achieve a high degree of automation of experiments. We also suspect that such algorithms can even exceed human abilities to analyze and interpret microscopy data," explains CISPA faculty Prof Dr Mario Fritz.
If the researchers succeed in combining the biological model system of HIPS with the modern machine learning approaches of CISPA, their safety could thus be efficiently tested at a very early stage in the development of new drugs. The project will also extend the knowledge gained to more complex developmental disorders, such as the detection of heartbeat rates and arrhythmias, enabling a comprehensive toxicological evaluation of drug candidates.
The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) was founded in 2009 as one of the first Helmholtz institutes nationwide by the Helmholtz Centre for Infection Research (HZI) together with Saarland University. Located on the Saarbrücken campus, HIPS is the first public research institute in Germany explicitly devoted to the pharmaceutical sciences. Their focus is on the development of novel anti-infectives and the improvement of their applicability to humans (translational research).
CISPA Helmholtz Center for Information Security is a large-scale federal research institution within the Helmholtz Association. Its scientists research information security in all its facets. They conduct cutting-edge basic research as well as innovative application-oriented research and work on pressing challenges in cybersecurity, artificial intelligence, and data protection. CISPA research results find their way into industrial applications and products that are available worldwide. In doing so, CISPA strengthens the competitiveness of Germany and Europe. It also promotes talent and is an elite school for excellently trained specialists and executives in the industry. In this way, CISPA also carries its know-how into the future.