Qfx1uc21qaagbyd2ejek grande

Biobide

4 Orders Completed
Donostia, ES

About Biobide

Biobide is a Contract Research Organization with more than 15 years of experience providing toxicity and efficacy studies with zebrafish animal model to Pharma, Biotech, Chemical, Cosmetic, Nutraceutical and Tobacco companies under Good Laboratory Practices (GLPs) environment and 3Rs.


We are specialized in developing tailor-made solutions based on customer's requirements. Thanks to our automated and innovative tools, we have developed and validated several High Content Screening (HCS) fast and cost-effective assays as well as generated different disease models in zebrafish:

- Target Validation with Morpholinos.

- Disease Models: genetic mutations, transgenesis and chemically induced models.

- Toxicity Assays: acute toxicity, neurotoxicity, teratogenic toxicity, cardiotoxicity, hepatotoxicity, ototoxicity, immunotoxicity, nephrotoxicity, behaviour alteration assay .

- Ecotoxicity Assays: Algal Microplate toxicity test, Daphnia magna immobilization assay, endocrine disruption assay in zebrafish and zebrafish larvae acute toxicity assay. 

- Efficacy Assays: Oncology (angiogenesis inhibition assay, target validation, cancer models generation), CNS (Neuroprotection, Epilepsy, Parkinson, Alzheimer...), rare diseases, metabolism, immune system, cardiovascular…

- Cosmetics: regeneration, melanin quantification and antioxidant assays.

Our Services (17)


ic

Drug Target Validation

Price on request

We carry out a transient inhibition of a particular gene/pathway with Morpholinos (MO) which is able to modify temporary a gene expression by knocking down the gene, for learning about the function of a particular gen or protein. Also, the zebrafish animal model allows combining different MOs at the same time to unravel possible synergistic effects between different genes.

Advantages: fast, statistically significant and high repeatability.


ic

Zebrafish Morpholino Injection

Price on request

We carry out a transient inhibition of a particular gene/pathway with Morpholinos (MO) which is able to modify temporary a gene expression by knocking down the gene, for learning about the function of a particular gen or protein. Also, the zebrafish animal model allows combining different MOs at the same time to unravel possible synergistic effects between different genes.

Advantages: fast, statistically significant and high repeatability.


ic

Zebrafish Models

Price on request

Biobide is specialized developing zebrafish disease models to be used in preclinical stages of Drug Discovery, for target identification or Drug Screening:

We have the ability to generate transgenic or mutant zebrafish models for different therapeutic areas through different technologies/techniques such as:

- Genetic mutations: CRISPR/Cas, TALENS or Zink fingers.

- Transgenesis: Tol2 kit.

- Chemically induced models


Examples of diseases models generated in Biobide: 

- Neurodegenerative disease models: Alzheimer's disease, Parkinson's disease, Epilepsy...

- Rare Diseases: DMD, HD, ALS…

- Oncology disease models: hepatocarcinoma, melanoma, digestive carcinoma...

Advantages: fast, homogeneous and high repeatability .


ic

Zebrafish Transgenic Services

Price on request

Biobide is specialized developing zebrafish disease models to be used in preclinical stages of Drug Discovery, for target identification or Drug Screening.

We have the ability to generate transgenic or mutant zebrafish models for different therapeutic areas through different technologies/techniques such as:

- Genetic mutations: CRISPR/Cas, TALENS or Zink fingers.

- Transgenesis: Tol2 kit.

- Chemically induced models

Examples of diseases models generated in Biobide:

- Neurodegenerative disease models: Alzheimer's disease, Parkinson's disease, Epilepsy...

- Rare Diseases: DMD, HD, ALS…

- Oncology disease models: hepatocarcinoma, melanoma, digestive carcinoma...

Advantages: fast, homogeneous and high repeatability .


ic

In vivo Acute Toxicity Studies

Price on request

Based on the OECD 236 Guideline (Fish Embryo Acute Toxicity test), a convenient, rapid and inexpensive acute toxicity test has been set up for screening purposes

Zebrafish embryos are incubated with 5 concentrations of the test chemical. Embryos are monitored and toxicity induction is measured as presence of specific endpoints: coagulation, heartbeat, somites formation and detachment of tail.

Advantages: cost and time effective assay to evaluate the acute toxicity of potential drugs at an early preclinical phase.


ic

In vivo Teratogenicity Testing

Price on request

Teratogenic studies must be performed in order to understand the potential of a drug to induce birth defects in offspring. ICH S5(R2) state the need to assess chemicals safety during the Drug Discovery and Development Process or before drug commercialization.

Developmental toxicity assay in zebrafish consists in two phases:

- Maximal Tolerated Concentration (MTC)

- Teratotoxicity Assay

Different organs and processes are analysed under a dissecting stereoscope, including teratogenic and toxic endpoints.

NOAEL, EC50 and LC5o are calculated and a Teratogenic Index (TI) established (ratio between LC50 and EC50) to conclude about the teratogenic potential of each compound.


ic

Ecotoxicity Testing

Price on request

- Miniaturized Algal Microplate Toxicity Test

Algae are extensively used as a biosensor for the evaluation of aquatic toxicity during the environmental risk assessment of chemicals. The purpose of this test is to determine the effects of substance on the growth of the freshwater microalgae through a miniaturized version of the alga growth-inhibition test (OECD 201). Exponentially growing test organisms are exposed to the test substance in batch cultures over a period of normally 72 hours. Growth and growth inhibition are quantified from measurements of the algal biomass as a function of time.

Advantages: increased simplicity and cost-effectiveness for high-throughput screening of aquatic toxicity of compounds during early phases or their development.


- Daphnia magna Immobilization Assay

The objective of this assay is to assess the acute toxicity of the test substances to Daphnia magna defined by the OECD 202. Young daphnids are exposed to the test substances at a range of concentrations for a period of 48 hours. Immobilization is recorded at 24 hours and 48 hours and compared with control values. The results are analysed in order to calculate the EC50.


- Endocrine Disruption Assay in Zebrafish

Biobide has developed a Thyroid Hormone Disrupting Chemicals (TDCs) screening assay for the identification of potential Thyroid Disrupting substances using zebrafish embryos as alternative model.

The TDC screening method comprises three assays: an initial Maximum Tolerated Concentration test (LC50, EC50 and EC10), the Thyroid Disruption Fluorescence assay (tg:mcherry) and a gene expression analysis to obtain more extensive characterization of the thyroid disruption effect.

Advantages: specific expression, high sensitivity and concentration-dependent response.


ic

In vivo Hepatotoxicity Testing

Price on request

Because of functional similarities between zebrafish and mammalian livers and the expression of different enzymes involved in liver detoxification, the zebrafish model is proposed for prediction of hepatotoxic agents.

Potential hepatotoxic effects can be assessed in a pluri-cellular and multi-organ context in a short period of time. Moreover, the concentration that is inducing toxicity can be measured by bioavailability assays.

Specially, acute hepatic toxicity is a rapid assay that can help to classify potential hepatotoxic compounds and can be easily detected through liver opacity assessment or fluorescence intensity evaluation. Additionally, zebrafish potentiates assessment of other hepatotoxic endpoints, such as steatosis, expression levels of genes related to hepatic metabolism or liver alteration assessment through histopathology.


ic

In vivo Cardiotoxicity Screening

Price on request

Zebrafish strain expressing Green Fluorescence Protein obtained from crossing adult zebrafish under strict environmental conditions of temperature and photoperiod is used. After being treated with different concentrations per compound, embryos are analysed. A 15 seconds video of the beating heart is recorded and analysed using non-commercial Cardio v3.0.0.5 software (Biobide property) to obtain the heart rate, the presence of arrhythmia and the absence of heartbeat (death/fibrillation).

Zebrafish cardiotoxicity study is an alternative, rapid and non-invasive assay with good sensitivity (100%) and specificity (93.3%) that is suitable to be used to early evaluate cardiotoxicity.


ic

In vivo Immunotoxicity Testing

Price on request

Zebrafish is a unique model for pharmacological manipulation of the innate and adaptative immune response. They are small and permeable to many small compounds and there are several transgenic lines available to visualize immune cells.

Biobide has developed a screening assay for the identification of potential immunotoxic/immunosuppressant substances using zebrafish embryos as alternative model. The assay is composed of four consecutive steps:

- An initial Maximum Tolerated Concentration test.

- Quantification of leukocyte population using two transgenic lines (mpx:GFP and mpeg:mcherry).

- Neutrophil migration assay.

- Gene expression analysis evaluated by qPCR.

The zebrafish embryo model enables a time- and cost-effective assessment of the potential immunotoxic and/or immunosuppressant effect of chemicals.


ic

Ototoxicity Testing

Price on request

Biobide has developed a method to detect in zebrafish the capability of a compound to induce ototoxicity as part of safety and pharmacology studies.

As well as hair cells, zebrafish has superficial mechano-sensory organs, called neuromasts, present on the lateral line along the head and body. Hair cells in zebrafish neuromasts are similar in structure and function to the inner ear hair cells in mammals. Similar to the processes involved in degeneration of hair cells in the organ of Corti in mammals, neuromast hair cells in zebrafish have been shown to undergo programmed cell death.

Zebrafish wild-type embryos are treated with different compounds and concentrations and then are incubated. Embryos are stained with DASPEI in order to visualize and analyse the number of neuromasts. We take photos and the pictures we obtained are analysed and corresponding IC50 is calculated.


ic

Animal Cognition & Behavior Tests

Price on request

Alterations in the mobility pattern of larvae induced by known drugs have been observed to strongly support the zebrafish as a predictive model of neuroactivity in humans.

Biobide has set up an assay to evaluate general behavioural alterations, based on responses to dark-light changes. After being treated and being tracked, zebrafish embryos will be visualized under a stereoscope to assess the following items: embryo viability, severely affected, swim bladder formation, presence of oedema, body shape defects and loss of equilibrium. Over 10 parameters are measured based on distance, velocity, movement duration and frequency.

Behavioural alteration analysis is an alternative, rapid and non-invasive assay with good sensitivity (95%) and specificity (100%) that is suitable for use in early neuroactive drug screenings.


ic

Acute Kidney Failure Models

Price on request

Biobide provides nephrotoxic assays to study kidney alterations and functional assays through morphological changes and fluorescent assays. It is worth noting that zebrafish secretion and reabsorption of particular molecules are carried out in a similar way as mammal nephron tubules. Furthermore, kidney development and function largely depend on the same orthologous genes for all vertebrate kidneys.

Evaluation of kidney injury can be assessed in zebrafish through different assays:

- Pronephros development assessment through wt1b::GFP transgenic line (pronephros-specific GFP expression)

- Kidney functional assessment through rodamine dextran clearence

- Proteinuria through lfabp::Vdbp-GFP transgenic line (Vitamine D-Binding protein (Vdbp) fused with GFP expressed in the liver and secreted into blood)

We also offer efficacy studies in zebrafish for specific kidney diseases.


ic

In vivo Angiogenesis Assays

Price on request

Biobide has developed a method in zebrafish to detect the capability of a compound to inhibit angiogenesis as part of efficacy pharmacology studies. Major molecular pathways regulating angiogenesis in mammalian systems (vascular endothelial cell growth factors, fibroblast growth factors, ephrin receptors, angiopoietins, etc) are conserved in zebrafish.

In our automated assay, a transgenic zebrafish line with fluorescent (cop-GFP labelled) is used to facilitate the visualization and analysis of the intersegmental vessels. An image analysis is carried out semi-automatically to evaluate the efficacy of different compounds and two different parameters are quantified:total number of intersegmental vessels and the number of intersegmental vessels that are complete.


ic

Neurodegeneration Animal Models

Price on request

At Biobide, we have validated zebrafish efficacy studies for the following rare neurodegenerative/neuromuscular diseases:

- Amyotrophic Lateral Sclerosis (ALS): Biobide offers two zebrafish transgenic lines expressing fluorescent protein DsRed under heat shock protein 70 promoter, making it a suitable model as a drug screening system: fluorescence intensity screening assay in the zebrafish whole body and/or by cell disaggregation:

• SOD1 G93R: transgenic zebrafish overexpressing mutant Sod1.

• C9orf72: transgenic zebrafish overexpressing mutant C9orf72.

- Duchenne muscular Dystrophy (DMD): dmdta222a (sapje) is a dystrophin deficient zebrafish mutant. Assessment of zebrafish muscle/behaviour is carried out with different techniques: birefringence analysis (visualization of myofiber integrity), immunofluorescence assay (Mandra1 antidystrophin antibody) or functional measurements such as Touch Evoke Escape Response (TEER).

- Dravet Syndrome (DS): Zebrafish didys552 line harbouring a point mutation in the scn1lab gene. We perform a high-throughput drug screening strategy through automated locomotor activity analysis.

- Tauopathy: we use transgenic zebrafish that overexpresses human TAU and DsRed under HuC (postmitotic neurons) promotor. A suitable Tau transgenic zebrafish model to screen GSK3β inhibitors.

- Chemically induced models

• Parkinson’s disease: MPTP or 6-OHDA induced models for the evaluation of drug effectiveness.

• Epilepsy: PTZ treatment induced epilepsy-like behaviour in zebrafish embryo for antiepileptogenic drug screening.


ic

Cosmetic and Personal Care Product Testing

Price on request

The use of animals for cosmetic experimentation is banned, demanding other alternatives, in order to evaluate compound’s safety and efficacy. Zebrafish is not considered an animal until its 5 days post fertilization, theregore appears as an option for replacing superior animal experiments.

- Regeneration Assay

Due the high regenerative capacity of the model, the zebrafish is selected to evaluate whether its regenerative potential upon new specific active ingredient or mixes could reach an increase in its regenerative capacity.

Zebrafish is used to evaluate whether its regenerative capacity is increased in presence of a test compound.

After 24 hours of treatment, individual embryos are visualized under the microscope and pictures are taken. Tail surgery is performed upon 48 hours post fertilization embryos are sedated and pictures taken to register the injury. Tail measurement is manually performed at different time points and compared with the control group.


- Melanin Quantification Assay

The zebrafish pigment pattern model provides the opportunity to study melanocyte development and melanin genesis, being an effective model to evaluate whitening capabilities of active ingredients/cosmetic products

Zebrafish pigment pattern allows to study melanocyte development and melanin genesis.


- Antioxidant Assay

Zebrafish has appeared as an effective model to evaluate antioxidant capabilities. Zebrafish larvae allows to study the protective properties of cosmetic active ingredients against external factors.

Moreover, safety pharmacology screening, biochemical stability testing or in vivo cytotoxic performance testing can be done with this model.


ic

In vivo Bioavailability/Bioequivalence Studies

Price on request

The objective of this study is to determine the real exposure of the treated zebrafish embryos to the drug compound in order to discard false negative results throughby liquid chromatography and mass spectrometry (LC/MS/MS). This service can be requested together with any other toxicity/efficacy study we offer.

Zebrafish

Not finding what you're looking for?

Get info on this provider's capabilities without requesting a quote.
AA

Ane Altuna

Business Development Manager
AA

Ainhoa Alzualde

Senior Study Director
OJ

Oihane Jaka

Study Director
MM

Maria J Mazon Moya

Study Director
AM

Arantza Muriana

R&D Management Director

FileType/PDF Created with Sketch. Biobide_General Presentation 2019.pdf

Click to Download

Biobide has not received any reviews.

Biobide has not received any endorsements.