The Zebrafish Lab have been the first ever to manage to reproduce a human infectious disease in zebrafish – a model organism whose system allows the detection of new antimicrobial agents.
You may have seen them before in aquariums. Their striking black and white stripes evoke the African savannah. Did you know that the so-called zebrafish share more than 75% of the human genome? Their genetic similarity to humans has made them an alternative (albeit not yet a replacement) to mammals in new drug research and development. Mice, the most commonly used species have a genetic similarity to humans that is only 5% higher than that of zebrafish, although they do have lungs. But that has not been an issue for The Zebrafish Lab who, in an unprecedented event, have been able to replicate pneumonia in zebrafish.
This is a remarkable feat which enables them to offer the world a unique service focused on researching not only new compounds with antibacterial and antifungical potential, but also new therapies, such as those which use antibodies.
Roberto Díez-Martínez had almost completed his PhD at The Rockefeller University when he detected the potential for research of these tiny fish. “All drugs must be tested” he states, “but legislation is becoming more and more restrictive regarding the use of mammals”. Less than two years ago, he returned to Pamplona (a town located in Navarra, Spain), where he created his own company together with Iranzu Lamberto and Rubén Díez in order to satisfy market needs.
In vivo trials with zebrafish have proven to increase the success rate of one compound and also decrease the risk of failure resulting from adverse side effects in the process of researching and developing new drugs. The cost of maintaining zebrafish is between 10 and 100 times lower than the cost of keeping laboratory mice. Furthermore, zebrafish require less amount of compound for testing (less than one milligram vs the two grams needed for mice). That is why The Zebra Fish Lab model is 70% more profitable than trials with mammals. Moreover, it reduces experimentation times and offers the chance to work with a significantly smaller sample of animals.
Díez-Martínez highlights the fact that their system cannot yet replace traditional systems for the time being. Therefore, their model works as a first stage of screening. If the test does not work, then a different research path should be followed. “We have a client who calls us project hitmen”, he says. “We know beforehand whether projects are viable or not”.
One of the main operating areas of The Zebra Fish Lab is oncology. Its platform ZebraOncoFish produces ‘dynamic’ visualizations of the cancer development process with zebrafish in vivo. This allows for the opportunity to design personalized treatments for each particular case. Their goal is to be able to develop a more personalized medicine. The company collaborates with the University of Navarra and CSIC (Spanish National Research Council) in trials that use different compounds on zebrafish which have been previously injected with tumor cells in order to find new solutions. This is especially the case for some cancer typologies, such as Acute Myeloid Leukemia. The company’s second area of attention is the development of new antimicrobial agents. In this field, The Zebrafish Lab has successfully developed pioneering technology. The team have been the first to reproduce a human infectious disease – pneumonia – in zebrafish. How? “by creating a sepsis (an infection) with bacteria in the gills”, Díez-Martínez explains.
Therefore, the company is now able to reproduce human infectious diseases in zebrafish, especially multi-drug resistant strains which have no cure at the present time. Bacteria are reproduced and injected into zebrafish in order to prove which drug is more effective. “We use compounds from FDA-approved Drug Libraries already available on the market, but which are currently used to target other diseases”, he says.
The startup company from Navarra already boasts bothpublic and private clients at national and international levels. For instance, an American manufacturer uses its technology to develop new functional food. This is proof that the use of zebrafish is not limited to healthcare. Indeed, in the environmental field, they are working on its use as a biometer for water pollution. The company collaborates with the Government of Navarra in a project to determine whether the water used for irrigation (that ends up in rivers) contains pesticides.