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In COPD awareness month; time to stop smoking cigarettes, whether you’re a mouse, a dog or a human!

5 November 2019

Image © NIEHS Steve McGraw

Rats jammed face first into what look like small milk bottles, no room to move, no option to even turn their heads. The rats in glass cylinders are arranged rows deep, screwed into a huge central metal cylinder that will provide a constant stream of cigarette smoke, directed into their faces in what is known as the ‘nose-only’ exposure technique. Mice contained in small plastic boxes for hours on end, flooded with a constant stream of cigarette smoke at a rate of 10 cigarettes per hour, with no break. This is the ‘whole body’ exposure model. Dogs trapped, immobilised, their noses strapped into masks, their eyes just visible peeking above. Or how about mice, with patches shaved on their backs, cigarette tar painted onto the bare skin until tumours appear? Tobacco distillate rubbed into a rabbit’s skin? The toxic compounds we now associate with smoking-related disease fed to rats until they develop fatal oesophageal tumours? These approaches have all been used to examine the effects of cigarettes, and shockingly, many are still used today.

[Read more…]

Stem cells cultured from human skin used to study fatty liver disease

1 October 2019

Non-alcoholic fatty liver disease comprises a range of conditions, ranging from the uncomplicated – hepatic steatosis – to the more severe hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease in which there is hepatitis and liver cell damage, in addition to fat build-up. NASH may lead to cirrhosis or liver cancer and affects millions of people worldwide. To date, no drugs have been approved to cure NASH and the major obstacles in the development of high-potential anti-NASH drug candidates are the identification of possible drug targets and the lack of adequate NASH models.
Several animal models have been developed to study NASH, using genetic modifications, dietary-induced disease or a combination of these. However, due to the heterogeneous pathology of NASH, most animal models do not accurately represent the human condition and there is a need to develop new models that are more human-relevant and human-predictive than animals. Now, a team of innovative researchers at Vrije Universiteit in Brussels – led by Dr. Robim Rodriguez and Professor Tamara Vanhaecke – aims to find whether using stem cells grown from human skin will lead to better models for NASH that may indicate where to target more effective treatments.
 
[Read more…]

Research round-up: Species-specific differences in the cerebral cortex revealed, a new retina-on-a-chip model and a functional microphysiological pancreas.

25 September 2019

Our October edition of Research Round-up has collected three very different advances in our understanding of human organ systems. In the Nature article “Conserved cell types with divergent features in human versus mouse cortex,” Hodge et al. analyzed the cellular composition of the human cortex at the single nucleus RNA level. In the eLIFE paper “Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human Retina-on-a-Chip platform,” Achberger et al. demonstrate the creation of a sophisticated retina-on-a-chip with vasculature-like perfusion, which can recreate drug-induced retinopathy. Gleiberman et al. describe the development of a microfluidic pancreatic islet-on-a-chip to accelerate efforts to study and develop effective treatments for diabetes, in their latest paper “Synchronized stimulation and continuous insulin sensing in a microfluidic human Islet on a Chip designed for scalable manufacturing.”

[Read more…]

Standing with Vanda- supporting the stance against unnecessary animal testing

8 August 2019

Intermittent or chronic nausea. Bloating. Burning, shearing or gnawing abdominal pain.  A feeling of fullness after eating just a few bites. Poor appetite and weight loss. These symptoms add up to the distressing condition known as gastroparesis – a chronic, life-limiting disorder that leads to weight loss and potentially life-threatening complications.  Gastroparesis is characterised by delayed gastric emptying and, while it is often associated with type 1 diabetes, most cases are idiopathic. There are no cures, only treatments, and some of those are less than satisfactory – posing risks of serious side effects and losing potency over time.

[Read more…]

Research round-up: Reliable 3D brain organoids, promising new FDA-approved drugs for treating lymphoma and an efficient cartilage-on-a-chip for screening disease-modifying osteoarthritic drugs.

19 July 2019

This edition of research round-up reports on very different aspects of applying human-focused technologies and strategies.  The paper by Velasco et al. entitled ”Individual brain organoids reproducibly form cell diversity of the human cerebral cortex” and published in Nature shows that results obtained from brain organoids are reliable and can be replicated.  In their paper ”Phosphorylation of SOCS1 inhibits the SOCS1-p53 tumor suppressor axis” published in Cancer Research, Ferbeyre et al. unveil the molecular mechanisms that turn a tumor suppression gene into an oncogene and suggest that an FDA-approved drug may stop this oncogene. Lastly, the study “Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip” published in Nature Biomedical Engineering by Occhetta et al. reports on the development of a human cartilage-on-a-chip to be used for screening new drugs for Osteoarthritis.
[Read more…]

Move over monkeys: combatting the world’s deadliest infections using groundbreaking human-mimetic tools

7 July 2019

A new article published in the journal Frontiers in Cellular and Infection Microbiology shows that research built around human-mimetic tools are more likely to succeed in the search for effective treatments for and prevention of flavivirus infection as compared to research using monkeys or other animals as laboratory models. The study, led by Dr. David Pamies at the University of Lausanne (formerly of the Johns Hopkins Center for Alternatives to Animal Testing), with researchers at Johns Hopkins University and the National Institute of Allergy and Infectious Diseases’ Vaccines Research Center in the U.S., carried out a comprehensive review of the models used to study deadly mosquito-borne flaviviruses (MBF) such as dengue fever and the Zika virus, known to cause neurological disease in humans.

The authors report that the host specificity of viral diseases presents a challenge for studying these human viruses in animals. Vaccines that had proved successful in primate tests have failed in human trials, leading to intense research using knockout and humanized transgenic mice. Thus, human genes relevant to the capacity of the virus to infect humans have been inserted into mice, but these modified animals are still mice, and the authors recognize drawbacks to this approach: “… several factors are recognized to influence the susceptibility of mice to MBF infection that limit applicability to humans.” For example, mice fail to display human disease symptoms if bitten by an infected mosquito (the human route of infection), and the mouse immune response varies depending on the animal’s age. Furthermore, the experiments are not reproducible in different laboratories – often an issue in animal experiments. [Read more…]

Korea’s first cross-ministerial forum to discuss new legislation supporting non-animal approaches

30 May 2019

Korea’s first-ever public forum to discuss replacing animal use in science will be hosted in Seoul at the National Assembly on May 30. Organized by Humane Society International (HSI) and Korean lawyers’ group People for Non-Human Rights (PNR), the forum is co-hosted by members of National Assembly – In-soon Nam, Kyungmi Park, Wanju Park, Seong-gon Wi, Sangmin Lee and the Assembly’s 4th Industrial Revolution Forum.

Newly proposed legislation prepared by HSI and PNR focuses on establishing an inter-ministerial entity to promote non-animal approaches in the toxicological and biomedical fields. Currently, the support of alternative research is limited to the Korea Center for Validation of Alternative Methods (KoCVAM), while the majority of animal research is funded by other ministries across multiple sectors. While these ministries support small-scale research projects on testing alternatives, there is no platform for exchanging research information or for providing major funding for programs that promote non-animal approaches. This forum will discuss collaborative support for adopting 21st-century approaches in scientific research and development without animal suffering. [Read more…]

New report sheds light on the UK’s growing medicines discovery industry

21 May 2019

The 2019 State of the Discovery Nation report offers a revealing insight into the current status of the drug discovery community in the UK, clearly indicating that companies are beginning to leverage technological advances to improve the drug discovery pipeline.  The report is compiled from responses to survey questionnaires sent out to small and medium-sized enterprises (SMEs) in the UK by the BioIndustry Association in collaboration with the Medicines Discovery Catapult (MDC) to create a snapshot of the current situation. This is the second report of its kind and is focused on two key areas: artificial intelligence (AI) for drug discovery and complex preclinical cell models, or CCM.

SMEs are crucial in the drug discovery process, in terms of employment and the innovation that they bring to the process. In terms of clinical areas, cancer came out as the strongest, with almost half the SMEs analysed focusing on oncology and over 38 percent of drug assets in development aimed at this area. [Read more…]

Centre for Promoting Alternatives to Animal Experiments launched by Atal Incubation Centre at Centre for Cellular & Molecular Biology in Hyderabad, India

25 April 2019

Atal Incubation Centre (AIC) at the Centre for Cellular and Molecular Biology (CCMB), in collaboration with Humane Society International/ India (HSI/India), has launched the Centre for Predictive Human Model Systems, a centre dedicated to enable a paradigm shift in science by focusing on 21st century new approach methodologies instead of animal models. The centre aims to prioritize investment in human-based, non-animal methodologies in life sciences research in India. This will be done by establishing a multi – stakeholder think-tank that represents the growing body of expertise on new approach methodologies on a scientific and policy level. Keeping in mind the 21st century biomedical science and toxicology motive globally to break siloes and forge partnerships among the scientific community for better flow of knowledge, support for research and open-access publication of literature will be a focus of the centre.

“This centre is a natural alignment to AIC’s objective of supporting new innovation and technologies. This sector of predictive human biology is ripe for investment and I am certain that this partnership with HSI/India will kindle the much-needed investment in this field,” said Dr Madhusudan Rao, CEO of AIC – CCMB. [Read more…]

Research round-up: 3D oral mucosa models, diabetes in a dish, and tubuloids from human kidney

12 April 2019

Every day we come across innovative, intelligent studies that do not rely on animals to investigate human diseases and that instead find efficient and cost-effective solutions in biomedical research that are human-focused. In this edition of Research Round-up we highlight three papers from scientists who have developed novel human-focused models to mimic the oral mucosa as well as to study diabetes and renal disease.

A model of the oral mucosa

A new study shows that it is now possible to study human oral mucosa using a 3D model created in the lab. According to the authors, this new model is a promising alternative to animal testing and brings new possibilities to the field of regenerative medicine. [Read more…]

Putting people first – human-relevant research for Parkinson’s disease

3 April 2019

World Parkinson’s Day (April 11th) aims to raise awareness of Parkinson’s disease (PD) and the desperate need for effective new treatments. A recent review authored by members of the BioMed21 Collaboration identifies advances that could be implemented to better understand pathological processes, improve disease outcome, and reduce dependence on animal models.  Many people may not be aware of how animals suffer in labs, used for research into Parkinson’s disease, when the answers we need may lie with patient-centred research and not animal testing.

For people, muscle tremors, or loss of fine control of movement, may be the first outward sign of Parkinson’s disease, but these motor symptoms are not the start. The death of dopamine-producing neurons in the brain ultimately cause the tremors, but the damage starts long before the tremors are apparent. Modelling this gradual loss of neurons is not possible in animals. Simulation of Parkinson’s disease in animals often uses injections of toxins directly into the brain. This destroys the dopamine-producing neurons, but the effects are instant and short-lived, compared to the slow progressive decline that occurs over decades in people. [Read more…]

For finding better treatments for TB, the computer is mightier than the mouse

13 March 2019

In March of 1882, Robert Koch used tissue from infected guinea pigs to show that the lung disease tuberculosis (TB) is caused by the organism Mycobacterium tuberculosis. At that time, TB was a constant presence in the population, infecting between 70 to 90 percent of people in urban areas of Europe and North America. Nowadays, although the mortality due to TB has reduced in developed countries, it remains a huge health issue and March is recognised globally as TB Awareness Month. In fact, the disease is still the leading cause of infection-related death worldwide, with up to one-third of the human population having latent TB.

Mice are resistant to TB, so in nature, you would never find a mouse with TB infection. Sadly, this does not save them from a life of laboratory experimentation. To get around their natural immunity, researchers manipulate mouse genetics, deleting mouse genes, and sometimes adding human genes, in order to create a TB-susceptible mouse. Whilst these manipulations are designed to make it easier for researchers to infect mice with different human diseases, this approach doesn’t necessarily create accurate and predictive models of the human condition. There is also huge wastage in this approach. For example, for one study requiring 50 genetically defined animals, 84 female “breeder mice” are used to produce a total of 400 animals, of which 350 are simply discarded and killed, being surplus to requirements. This over-breeding to generate animals with the requisite, manipulated genetics is not isolated to TB research – it is a strategy used throughout medical research. [Read more…]

Modelling the human heart: Predictive models for cardiotoxicity testing

22 February 2019

What do self-driving cars, solar airplanes and renewable energy have in common with the human heart? At first thought, not a great deal, yet a recent scientific endeavour called the Living Heart Project has brought together experts in engineering, aeronautics and energy to produce a sophisticated new model of the human heart for use in medical research. This 21st century approach to understanding heart disease is vitally important and of particular relevance in February – American Heart Month. Heart failure is a serious problem affecting 26 million people worldwide; heart disease causes 1 in 4 deaths annually in America. It can occur at any age, but becomes more common as we get older. Plus, different forms of heart failure affect men and women differently and require different treatments.

Efforts like the Living Heart Project are long overdue, survival rates for heart failure patients have not improved since the 1990s. Despite a half-century of research funding and countless rodent experiments, translation of animal data to people has been poor to non-existent. Not surprising perhaps, considering the differences in size and development, heart rates, oxygen consumption, contractility, protein expression, and stem cell populations between humans and rodents. Calls for ‘improved animal models’ for human heart disease favored larger animals – such as dogs – due to closer resemblance of cardiac physiology between dogs and humans (compared to rats and humans). Experimental induction of heart failure in the young, healthy dogs employed as models is severe – often requiring complex, extensive surgery – and distressing.  In addition to these ethical concerns, there are scientific reasons to move away from canine models of heart failure – the collateral coronary circulation in dogs creates inconsistency and heterogeneity in the response to myocardial lesions which make comparison of post-injury outcomes difficult. [Read more…]

EU ORCHID project interim roadmap lays out the route for organs-on-chips

18 January 2019

Organ-on-Chip in Development (ORCHID) is a European Horizon 2020 project that aims to capitalise on the innovative technology that is organ-on-chip, or OoC. The ORCHID consortium is made up of seven partners from six European countries and was launched in 2017 with the overall aim of building a network of OoC stakeholders, including academic, research, industrial and regulatory institutions, in order to move OoCs from laboratories to a more global awareness and utility.

We are in the midst of a ‘drugs drought‘, which means there could be no more new, approved compounds by around 2070 unless we radically alter the current drug discovery paradigm. Using animals as models of human disease for predicting safety and efficacy of novel drugs has proven to be time consuming, costly and about as effective as tossing a coin—with failure rates running as high as 99.6 % for some conditions.  While the reasons underpinning the failure of new chemical entities to reach the clinic, and successfully remain there, are complex and multi-factorial, there is no doubt that one of the greatest limitations for identifying new therapeutics for human diseases is the deficiencies in the animals employed/manipulated as models of the human condition.  [Read more…]

Launch of Indian Society for Alternatives to Animal Experiments

14 January 2019

In November 2018, India joined other innovative economies working to replace the use of animals in laboratory experiments with the launch of the Indian Society for Alternatives to Animal Experiments (ISAAE) during the country’s second national conference on alternatives in New Delhi. Humane Society International, founder of the BioMed21 Collaboration, was a lead sponsor and keynote speaker at the conference, which created a platform for national and international scientists from various backgrounds to engage in discussions pertaining to the present and future of alternatives to the use of animals in research and testing.

The chief guest of the event, Dr Renu Swarup, Secretary of the Department of Biotechnology, graced the inaugural ceremony with an encouraging speech for the audience, comprised of scientists and students alike. The informative keynote lecture by HSI Vice President of Research & Toxicology, Troy Seidle, kickstarted the event, focusing on the need for human biology-based pathways to study human diseases and test new products, and exploring the vision of expediting 21st century science through the BioMed21 Collaboration. [Read more…]

Improving diabetes outcomes through personalised medicine

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…]

Bioengineered human cardiac models spur disruptive innovation in disease research and drug discovery

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…]

Call for new approaches to fill significant gaps in understanding Parkinson’s disease

3 October 2018

Analysis published in Drug Discovery Today reveals the gap between animal models of Parkinson’s disease (PD) and our understanding of the neurodegenerative processes underlying the disease, and calls for the implementation of modern, human biology-based technologies to better understand pathological processes and improve treatment outcome.

While current approaches to drug discovery for PD have led to the development of tools for the motor symptoms that accompany neurodegeneration, they have fallen short of identifying preventative or curative therapies. The authors of “Parkinson’s disease research: adopting a more human perspective to accelerate advances” describe how this failure derives from the fact that animal disease models can never fully replicate the healthy or diseased human brain. Dr. Catherine Willett and Dr. Lindsay Marshall advocate new approaches with greater focus on recent advances in systems biology computer science and engineering using information from human cells, tissues, and subjects. [Read more…]

In silico mapping provides new insights on patient outcome in sepsis

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…]

Fatty liver disease pandemic needs ‘gold standard’ human- relevant research, say Belgian scientists

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…]

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