Alzheimer's is a terribly cruel disease. Its affliction rate is expected to triple over the next 40 years. What is worse, decades of intensive research have failed to yield a substantially effective treatment, and in 95 percent of cases the precise causes of the condition are still unclear.
A new scientific paper by Humane Society International's Dr Gill Langley published in the journal Drug Discovery Today argues that one likely reason for these failures is an over-reliance on laboratory-created animal 'models:' more than 300 potential treatments have been effective in mice and other species, but no breakthrough has emerged for human patients. With Alzheimer's being the number one cause of dementia in the elderly, affecting almost half a million people in the UK and more than 35 million worldwide, this lack of research progress is a waste of time and resources that we simply can't afford.
More than 300 potential treatments have been effective in mice and other species, but no breakthrough has emerged for human patients.
In Alzheimer's disease, brain cells progressively malfunction and die, causing memory loss, impaired judgment, language disabilities, disorientation, confusion and other changes. Ultimately fatal, Alzheimer's disease causes suffering over a long period of time to patients and their families.
Last year, a G8 summit on dementia agreed a significant increase in funding of dementia research and the development of an international action plan, with the goal of identifying an improved treatment or cure for dementia by 2025. However, unless the current research paradigm changes dramatically, these worthy goals are likely to fail.
Progress is urgently needed in understanding Alzheimer's disease and in finding effective treatments. Available drugs can help stabilise memory loss and confusion for a few months in about half of patients, but no preventative treatments exist and none that slow the inexorable development of the disease.
Despite Alzheimer's being a uniquely human disease, much research over the last two decades has been conducted using genetically modified mice. The outcome of this multi-billion pound exercise has been a series of failed clinical trials: no new therapies have reached the market for a decade.
Just from a common-sense perspective, it's hardly surprising that research using mice has not been successful in finding effective treatments for a human illness that impacts uniquely human complexities of memory, thought, behaviour and language.
The so-called mouse models cannot replicate all the characteristics and underlying causes of human illnesses like Alzheimer's disease, and their medical value is severely limited by insuperable species variations. Key differences between mice and humans are found at all levels--genetic, molecular, cellular, organ and behavioural. The mainstream approach based on animal 'models' of human disease has been deeply disappointing, not only in Alzheimer's disease research but in other illnesses too.
It's time for a paradigm change. Scientific and technical developments emerging in the 21st century provide the tools for transitioning to a next-generation, more successful era of research, based on human--not animal--biology. A new roadmap for Alzheimer's disease research would involve a conceptual and practical shift away from the current focus on animal models (with its emphasis on re-creating selected clinical symptoms in other animal species often without due regard to cause), and more strongly towards understanding the dynamics of disease pathways in human species-specific models.
A fresh vision for disease research should challenge the existing animal-based paradigm and incorporate novel and emerging scientific tools and models into a re-shaped strategy fit for this century. A transition of this kind is already happening in safety testing, and to exploit the best science a structured change is needed in health research too.
Disease pathways identified in human in vitro systems (such as three-dimensional stem cell-based tissue constructs) will provide more relevant and mechanistic information, including a cell-level understanding of how initiating genetic or environmental events combine to cause diseases like Alzheimer's.
Once this dynamic process is better understood, key aspects of disease pathways can be targeted with novel drugs in the test tube. Ever-improving brain imaging technologies are yielding real-time clinical data from patients. This is being integrated with genomics, cellular and computer modelling studies to provide a global understanding of human disease processes, with the help of systems biology.
Incorporating these and other 21st century approaches into a revised, coherent, modern framework offers the best chance to overcome existing bottlenecks in the effective prevention and treatment of Alzheimer's disease. As in the field of safety testing, technology is driving the change and the benefits are likely to be substantial. By moving the focus of research away from misleading mouse biology and onto human biology, the scientific quality and clinical relevance of research into Alzheimer's and other human illnesses will improve, reducing late-stage and expensive drug failures.
As long as research into this devastating illness continues to be dominated by the animal 'model' paradigm, we'll keep finding out more about the brains of genetically modified mice; but we'll be as remote as ever from finding desperately needed safe and effective therapies for Alzheimer's patients.
Find out more at hsi.org