ZeEfficacy

Testing drug efficacy using zebrafish disease models

Efficacy studies based on zebrafish

In the early stages of the development of a new drug, all regulatory agencies focus their interest in safety studies, so they are usually comparatively less demanding in terms of characterization of the compound's effectiveness, allowing to provide information about the mechanism of action of the compound in order to justify the patients exposure to this new therapy. On the other hand, the promoter of the compound is the first interested in knowing its effectiveness before reaching clinical development, where the increase in costs is dramatically significant.

In addition to the traditionally used models, rodents, pigs, dogs and non-human primates, some of which must necessarily be included in regulatory validity toxicological tests, there are other models, vertebrates and invertebrates, whose inclusion in pre-clinical development must be not only considered, but probably regulated within a short time.

Danio rerio (zebrafish) is one of the new models of vertebrates most used in recent years. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. Zebrafish embryos are transparent allowing direct evaluation and "in vivo" effect of the drugs on organs and tissues. The zebrafish is easy to breed and maintain, and fertility is high (each female can produce 100 to 200 eggs per mating, offering a large number of animals to test). Since the zebrafish has mammal-like organs, it turns out to be a much more useful model than other alternative models for the study of the function of genes and the effect of drugs on humans.

Summarizing, zebrafish allows us to performe efficacy tests "in vivo" faster, more accurate and more profitable.

 

 

Neuroprotection model

Fact: Neuroprotection is the mechanism of preservation of the correct numbers of neurons and their functionality damaged and progressively reduced in several central nervous system (CNS) disorders including injury, stroke and also neurodegenerative diseases and acute management of neurotoxin consumption.

Aim: Assessment of neuroprotection caused by NOEC of new drugs in zebrafish larvae.

Method: We will use Danio Vision system to test zebrafish “circadian” motor activity in light and dark phases. The Daniovision system from Noldus allow us to perform circadian locomotor study with up to 96 individual embryos at time, meaning 5 different experimental conditions with about 20 animals/condition or drug doses.

Cardioprotection model

Fact: The search for therapies that increase cardioprotection of patients at risk of cardiovascular accident is one of therapeutic areas of greatest interest to the medical community and industry pharmaceutical.

Aim: Assessment of cardioprotective potential of new drugs in zebrafish larvae.

Method: Incubation of 10 dechorionated larvae of transgenic GFP heart fishes at 5 dpf with NOEC concentration of the molecule of interest during 4 hours in combination with the Doxorubicina, a cardiotoxic molecule. At end point every larvae heart and vessels are imaged during 1 min and analyzed with ZeCardio system.

DMD (Duchenne Muscular Dystrophia) phenotypic screening

Fact: Zebrafish dystrophin mutants, sapje represent excellent animal models of human muscular dystrophy and it can be used to test new therapies.

Aim: ZeClinics proposes a phenotypic drug screening to discover novel therapies against DMD.

Method: Optical birefringence, locomotion, genotyping and immuno-hystochemistry techniques will be used to assess whether the drug tested is capable of reducing the effects of the disease onsapje  larvae.

ZeCUSTOM

Just tell us your biological/pharmacological question and we propose and run the best zebrafish-based scientific methodology and provide reliable results. Rare diseases, gene functions, biological pathways, drug-target interaction, drug accumulations and much more can be developed and studied in zebrafish.

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