How Zebrafish Imaging Can Support Precision Medicine

Zebrafish is a potent tool for precision medicine approaches to neurological diseases

One of the most promising modern treatments that offer hope to patients who have no suitable or available treatment is personalized medicine. Patient-specific therapies are required for prevalent diseases with a wide phenotypic spectrum and for rare and unidentified conditions. Understanding the underlying mechanisms and how to stop them are necessary for both situations. Despite the recent growth of novel therapeutic approaches, there is still a gap between the bench and bedside that needs to be filled in a patient-specific manner. Particularly in the context of neurological illnesses, the complexity of genotype-to-phenotype relationships has slowed the creation of effective disease-modifying medicines.

The development of treatments is greatly aided by the use of animal models of human diseases. Zebrafish are now recognized as an effective and practical model organism for simulating and researching a variety of neurological diseases. This model has received a lot of praise for being an invaluable resource for comprehending disease causes, behavioral investigations, toxicology, and drug screening. The capacity to adapt research from zebrafish studies and the vast potential of illness modeling in humans open the door to creating specialized therapeutic approaches. Zebrafish have the ability to forecast the development of unique, precise treatment techniques in neurosciences, highlighting the benefits and capacities of this in-vivo model to create specialized therapeutic approaches.

Zebrafish are powerful tools in the fields of developmental biology, genetics, and medicine. Their application fits into several significant tiers of the general precision medicine paradigm. As revolutionary genetic engineering and cutting-edge screening techniques continue to develop, their popularity, success, and usefulness will only increase.

Developing precise oncology treatments with zebrafish

The foundation of personalized medicine is each patient’s genetic, genomic, and environmental information. Risk assessment, disease diagnosis and molecular characterisation, disease prognosis, pharmacogenomics, tracking treatment response, and pathogen genomes are among the domains covered by this term. It occurs because it is possible that each patient will react to treatment extremely differently, say if you give the same medication to 15 people for the same type of cancer. Pharmacogenetics, pharmacogenomics, and genomic information found in databases are some of the current possibilities for individualized medicine. Access to many human genomic variations is possible because of databases.

Pharmacogenetics is “the science that studies how genetic variations in individuals affect their response to medications”, while pharmacogenomics studies the way that genetic variations affect drug development. The main benefit of these techniques is prevention. To do this, one must foresee a disease’s onset before the onset of its initial symptoms. Mouse patient-derived tumor xenograft (PDX) models are becoming more common. However, because of the expensive expenditures, the lengthy wait for results, and the laws governing the protection of animals used for research, working with mammals is not particularly simple. Due to these issues, researchers are searching for alternatives, one of which are zebrafish in instead of mice.

Zebrafish have shown to be a useful model for researching the biology of human cancer with the ultimate goal of creating new treatments. Danio rerio exhibit histological and genetic similarities with Homo sapiens and are susceptible to in-vivo imaging, high-throughput drug screening, mutagenesis, and transgenesis. Zebrafish are becoming increasingly important in the field of precision oncology. In fact, zebrafish models of cancer have been utilized to find tumor biomarkers, specify therapeutic targets, and offer an in-vivo drug development platform.

New zebrafish research is beginning to open the door to individualized clinical applications that are directed. Zebrafish have been successfully used as a real-time avatar of prognosis and drug response to determining the best course of treatment for a specific patient utilizing patient-derived cancer cell xenograft models. Zebrafish patient-derived xenografts are a fantastic way to practice personalized therapy. And why utilize zebrafish as a model organism rather than another one, such as mice? A significant benefit of employing zebrafish is that it offers a one-week experiment. Speed is crucial in these situations since the assay’s turnaround time must coincide with the time needed to make a clinical judgment. Furthermore, human tumor cells can be transplanted fairly early in the embryos due to the external fertilization and development of the zebrafish.

Zebrafish are actually being used more and more in laboratories as a result of their many benefits, including their ease of feeding and breeding, quick generation times, transparent eggs, and the fact that, up until 120 hours after fertilization, they are not covered by the European Union Directive on the protection of animals used in research. Zebrafish are helping to gradually decrease the number of mammals needed in studies because of their similarities and benefits. More than 5000 zebrafish mutations and transgenic strains have previously been identified, making them excellent candidates for transgenics.

Given the importance of zebrafish as a disease model, applications for its use as a precision oncology tool are beginning to be recognized. Studies using zebrafish cancer models have spurred this development by defining the molecular drivers of carcinogenesis, identifying actionable changes, and developing targeted therapeutics. The findings to date serve as a foundation for the research directions in personalized medicine as well as platforms, workflows, and systems for applications in precision oncology.

In the future, zebrafish may co-emerge with current clinical applications, such as genomic technologies and molecular diagnostics, to improve our ability to precisely tailor individualized cancer therapies and positively influence the clinical outcome of each patient afflicted with cancer. This is possible thanks to the array of existing and developing zebrafish models that make up the collective toolbox of the zebrafish and precision oncology research community.

Zebrafish embryos aid in the search for an effective precision leukemia treatment

The most prevalent cancer in children is leukemia, which is the catchall phrase for blood cancer. New therapies that are individualized for each patient and utilize the patient’s own tumor cells are required due to the complexity of leukemia and the inefficiency of existing therapies. 

The zebrafish continues to demonstrate that it is a viable alternative to experimental animals when it comes to the 3R’s principle (replace, reduce, refine), and it is beginning to play an increasing role in personalized medicine. To lower mortality in diseases like leukemia, tumor cell monitoring and metastatic, cell behavior research is crucial. 

For in-vivo examination of leukemia invasiveness, metastatic behavior, angiogenesis, and responsiveness to anti-tumor therapy, zebrafish appear to be an effective model.  They offer an excellent system to study blood and leukaemia because their larvae are completely transparent, enabling blood development to be seen in real time under the microscope.

Acute myeloid Leukaemia (AML) is the second most common form of childhood leukaemia. 

It is now well known that errors (mutations) in our blood stem cells lead to the development of AML. A large amount of research has been carried out to identify the mutations that result in Leukaemia and more than 250 mutations have been identified.It is known that a single mutation is not enough to cause Leukaemia; each child with AML will have between 5-20 of these mutations.

 In research project on the genetic causes of Leukaemia by UCL Cancer Institute,London,  Dr Payne and colleagues aim to create a system where they can test the roles of possible secondary drivers to see which are the most important in the development of Leukaemia.They use Zebrafish as a model system. Zebrafish develop Leukaemia in the same way as humans and the genes that are responsible for programming blood development are the same.

In a different study, Dr. Payne’s group is using automated Zebrafish screening for the discovery of new drugs for Acute Myeloid Leukemia. The group achieves automated analysis of thousands of drug compounds and applies the same approach for all their experiments to obtain novel insights in an efficient manner. 

Why are zebrafish AI-based image data analysis a key enabling technology?

With their transparent, rapidly developing embryos, zebrafish screening offers a unique opportunity for drug screening in living animals. This enables reasonably high-throughput, microscopy-based tests. Zebrafish screening has been used in drug screening, but its use has been constrained by the lack of quick, adaptable imaging and processing tools. These screens frequently rely on laborious human assays or the creation of customized automation solutions, both of which take time and knowledge to produce. 

IDEA Bio-Medical created an adaptable automated screening process that is simple to use and appropriate for high-throughput phenotype-based tests of live zebrafish. Our affordable, simple-to-use imaging system is accompanied by groundbreaking deep learning-based image processing to enable fully automated Zebrafish screening. Utilizing the adaptable and user-friendly Hermes and Athena HCS platform from IDEA Bio-Medical provides the ultimate automated solution for zebrafish screens.