13 December 2018

Diabetes treatment is often touted as the poster-child success of animal research; after all, insulin was first discovered in dog pancreas almost 100 years ago. A lot has changed since then. Or at least it should have. The reality is that billions of research dollars are still wasted on ineffective animal models of diabetes that are not translating to therapies delivering effective glycaemic control for patients. For instance, oral insulin and nicotinamide were both therapeutic interventions that showed promise in animals but failed in humans. A new review – ‘Future Roadmaps for Precision Medicine Applied to Diabetes: Rising to the Challenge of Heterogeneity’ – from clinical experts and published in the Journal of Diabetes Research, reveals the gap between animal models of diabetes and the human condition and calls for alternative, non-animal approaches to drive advances in research that are ‘clinically translatable’ and that apply existing and evolving methods of relevance to human focused research.

The crude experimentation with dogs in the 1920s provided us with a basic understanding of diabetes and it is clear that animals can only ever provide an incomplete understanding of disease. Research questions now are too complex to be answered by a model that superficially resembles the human condition; only human-focused models can answer the in-depth sophisticated questions that our improved understanding of disease have allowed us to formulate, and the explosion in biotechnology and the ‘omics revolution that have occurred in recent years are providing the human relevant tools to enable this. Shifting focus towards human studies has helped to reveal that diabetes is a multifactorial, heterogeneous spectrum of metabolic disorders with environmental and genetic elements, but it seems that a continued reliance on animal models has failed to provide a detailed understanding of disease pathogenesis or provide the elusive cures.  [Read more…]

23 October 2018

Thrombosis-on-a-chip, vasculature-on-a-chip and engineered models of human cardiac fibrosis are just a few of the new technologies revolutionizing research into human cardiovascular disease—a condition responsible for 17 million deaths per annum globally. A new study entitled Cardiovascular Disease Models: A Game Changing Paradigm in Drug Discovery and Screening, published this week in the journal Biomaterials by bioengineering scientists from the University of Toronto, proposes a new paradigm for research into cardiovascular diseases. The new paradigm is rooted in a human-specific understanding of disease mechanisms, coupled with application of novel microphysiological and computational tools based on human biology to create more predictive laboratory models of the human disease.

Lead author, Dr. Houman Savoji, CIHR & FRQNT postdoctoral fellow in Prof. Milica Radisic’s Laboratory, explained that, “In vitro and in silico disease models are frequently used to complement or confirm data acquired from animal models. However it is apparent that the application of these two fast-growing and emerging platforms, given their reduced costs, more ethical and more accurate, human-relevant outcomes, are becoming promising substitutes for animal models. The development of multi-functional platforms that combine mechanistic knowledge about the pathophysiology and etiology of cardiovascular diseases with ever-expanding engineering technologies (i.e., micro/nanofabrication) and advances in stem cell biology, brings hope to the mandate of improving translation in drug discovery and concomitantly reducing the use of experimental animals in preclinical research.” [Read more…]

21 September 2018

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a major public health concern, particularly for the very young and very old. Around the world, sepsis kills more people than AIDS, breast cancer and prostate cancer combined. The mortality rate can be as high as 50%, and those who survive are often left with long-term consequences that may include physical and psychological disabilities.

Sepsis becomes fatal as a consequence of multiple organ failure caused by an overwhelming cascade of inflammatory mediators released into the bloodstream. But exactly how this response to infection is regulated, and whether it is in fact a regulated response, remains uncertain. Some authors have suggested that the body goes through different immune states while fighting sepsis, starting by activation of immunity and then reaching immune paralysis or exhaustion. Current treatments have shown limited efficacy and patient outcome is in most cases unpredictable.  [Read more…]

9 August 2018

A new study by scientists from the Vrije Universiteit Brussel calls for a new gold standard in research to treat non-alcoholic steatohepatitis (NASH), an obesity-linked chronic liver disease impacting millions of people of all ages worldwide. The disease can progress to liver cancer if untreated, creating a massive strain on an already overburdened healthcare system. The study, published in Pharmacological Research, proposes a human-specific roadmap to better understand the biological mechanisms behind NASH, a crucial missing link in the effort to develop effective, and urgently-needed, treatments for the disease.

Dr Robim Rodrigues and Prof Tamara Vanhaecke of the Vrije Universiteit Brussel, lead authors on the study, commented that “In vitro models that reflect population diversity and specific mechanisms of the disease are already valuable tools today.” Modern techniques, including transcriptomics, proteomics, and metabolomics, are rapidly becoming more reliable and may therefore provide insights into the mechanistic background of NASH.” Dr Rodrigues explains that several drugs in development for NASH have been tested using in vitro models, clearly indicating the value of these systems in NASH R&D. He is optimistic that further development of predictive, human-based tools will provide a more cost-effective and reliable methodology for much-needed drug development for NASH liver disease.  [Read more…]