The need for advanced three-dimensional neural models and developing enabling technologies
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Biomaterials for 3D Cell Biology Prospective Article
The need for advanced three-dimensional neural models and developing enabling technologies Daniel Merryweather and Paul Roach, Department of Chemistry, School of Science, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK Address all correspondence to Paul Roach at [email protected] (Received 17 April 2017; accepted 23 June 2017)
Abstract Neurological and psychiatric disorders account for an increasing proportion of the global disease burden. Correspondingly the neuropharmaceutical industry has experienced a significant contraction in recent years resulting in a poor variety of therapies available to treat an expanding range of conditions. Perhaps the greatest contributor to this failure in drug-discovery is the lack of understanding of the underlying biology of the nervous system and how molecular scale events translate into macroscale pathologies. Due to the unique nature of the human nervous system commonly used model organisms are often poorly representative of human pathologies resulting in a need for the development of advanced in vitro models that are capable of faithfully modeling complex structures within the brain. In this prospective, strategies for the generation of neuronal circuits and cultivation of complex three-dimensional (3D) cultures are explored. Frequently these constructs provide valuable insights into systems and processes that are difficult to explore in vivo due to the isolated and delicate nature of neuronal tissues. New developments are required to assess the physiological functions of 3D tissues in vitro.
Introduction Neurodegenerative diseases and mental disorders currently present a huge burden to national healthcare systems, a burden that is predicted to become increasingly overwhelming as the Western population ages. As of 2004 mental and neurological disorders represented the greatest burden of disease in Europe[1] with up to 38.2% of Europeans suffering from some form of disorder in 2010, up from 27.4% in 2005.[2] As of 2010 the total cost of this burden was an estimated €798 billion with 60% of this figure resulting from direct costs of treatment and the remaining 40% due to lost productivity.[3] The approach to this daunting challenge has been somewhat variable, with international efforts to map the human brain and connectome underway in the US, EU, and China, along with attempts to raise awareness and diagnosis of mental disorders, both coinciding with a 70% contraction in neuropharmaceutical drug research programs over the 10-year period between 2002 and 2012.[4] The reasons for this contraction are varied, however major contributors include extremely low rates of drug candidates reaching phase I clinical trials, with just 8% of compounds reaching such a stage between 1993 and 2004,[5] along with poor assignment of manpower and capital. Primarily this lack of success is the result of a poor understanding of the underlying biology of neurodegenerative and mental health disorders, and a paucity of effective mo
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