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What is translational research?

Drug Discovery / 11 September 2020 / Zara Puckrin, BSc

In recent years, there has been an increased focus on the benefits of translational research. “From bench to bedside” has become a popular phrase which underpins the concept at its core. So, what are the benefits of translational research, and what makes a research model translational?


Definition of translational research

The aim of translational research is to predict clinical responses earlier in the drug discovery process. Research can be described as translational if it uses experimental models which more accurately mimic human physiology, such as ex vivo human tissue assays, 3D culture models, and induced pluripotent stem cell (iPSCs) derived models. Translational research, translational medicine, and translational science are terms used interchangeably, but they mean the same thing: better clinical outcomes for Pharma and its patients.


Why is translational research important?

The importance of translational research becomes obvious when looking at current drug failure rates. The financial impact of pharmaceutical attrition is huge, costing Pharma between $800 million and $1.4 billion per candidate. Animal models are considered the gold standard of preclinical research, yet today’s researchers are encouraged to reduce, replace, and refine their animal use in accordance with the Three Rs.

It is thought that by humanizing the preclinical models available to researchers, the efficacy and toxicity of drug candidates can be estimated more accurately, and the number of animals used can be reduced. 3D cell culture models (such as organoids and spheroids) have therefore become increasingly popular in recent years, alongside iPSC-derived human cell lines and human fresh tissue assays.

07AUG20 drug cost attrition failure discovery plainFigure 1: The cost of drug development is rising, with approximately 95% of compounds failing clinical trial. 


Examples of preclinical models transforming translational research

Below, we have highlighted two unique models championed by researchers for their ability to predict clinical responses early. Not only do these assays reflect the complexity of human physiology, but they can be customized to research a wide variety of diseases, whatever your area of research.


Human Skin Explant Assays by REPROCELL (Biopta)

Human skin explant assays are highly-specialized ex vivo models which use skin biopsies from living donors. In these assays, multiple full-thickness skin biopsies are suspended in transwells in vitro. With the dermis submerged in cell culture media, drugs are applied topically to the epidermis and left to incubate. The culture media is then collected for analysis where changes in inflammatory markers and other cytokines are measured.

Human tissue testing possesses the unique advantage of being able to investigate drug behavior at any stage of the drug discovery pipeline. One example of this is AMG 337, which nearly failed clinical trials due to headaches in participants but was rescued by human tissue research. Although a highly specialized area of research, there are a few contract research organizations that provide human skin explant assays, including AnaBios and REPROCELL (Biopta).

A researcher taking punch biopsies from human skin in a dish

Figure 2: A scientist taking full-thickness biopsies for a human skin explant assay


Skimune® 3D Skin Equivalent by Alcyomics®

Skimune® 3D is a full-thickness human skin model developed by Alcyomics® in collaboration with REPROCELL. Composed of primary human skin and autologous immune cells, Skimune® 3D is designed for testing immunological skin reactions. The 3D co-culture model uses Alvetex™, a microscopic scaffold that maintains cell structure in vitro while optimizing cell growth, differentiation, and function.

SEM Alvetex Structure-1Figure 3: Skimune® 3D uses Alvetex™ to maintain cell shape and physiology during culture.


Better translating your discoveries into therapies

REPROCELL (Biopta) is the leading provider of ethically sourced human fresh tissue studies and Alvetex™ technology. Through our global network of tissue suppliers, we can ethically obtain healthy and diseased tissue from your target population, including donors with inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), atopic dermatitis (AD), and more. Not convinced? You can find out more about the science behind our human fresh skin models below:

Induced psoriasis model
This experiment assesses whether your test articles cause a reduction in inflammatory cytokine release in psoriasis compared with a control compound, such as a ROR-ɣ inhibitor.

View psoriasis model →

Induced acne model (LPS)
This experiment explores whether your test articles cause a reduction in inflammatory cytokine release in acne vulgaris, with betamethasone as a reference compound.

View acne model (LPS) →

Skin inflammation model (PHA)
This assay uses healthy skin punch biopsies which are induced to display an inflammatory phenotype using phytohemagglutinin (PHA) to measure test article efficacy. 

View inflammatory skin model →

Induced atopic dermatitis model
This experiment assesses whether test articles cause a reduction in inflammatory cytokine release in atopic dermatitis, using a steroid as a reference compound.

View atopic dermatitis model →


References

Paul et al. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nature Reviews, Drug Discovery. 2010;9:203-214

Amouzadeh et al. Clinical Implications and Translation of an Off-Target Pharmacology Profiling Hit: Adenosine Uptake Inhibition In Vitro Translational Oncology 12:10 (2019)

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