The Ministry of Education, Culture, Sports, Science and Technology (MEXT) will launch a brain & neuroscience integration program in the next fiscal year. The 'Research Program on Brain and Mind' will be radically reorganized, and the program will be relaunched as a new six-year plan, aiming at producing novel therapeutic drugs for dementia, identifying biomarkers that lead to blood diagnostics, and developing a digital brain. Translating the knowledge acquired from basic research, such as identifying brain functionality, into the diagnosis and treatment of neuropsychiatric disorders, the program will encourage the following activities by mobilizing mathematical and information sciences: partnerships between basic researchers and clinical research; integration of various research fields, such as those in wet and dry science practices such as fusion of dry and wet researches; formation of industry-government-academia consortia; and participation by young researchers and researchers from across different fields. The FY2024 budget request amounts to 9.3 billion yen.
With the super-aging of Japan's population, the number of patients with dementia has increased from 4.62 million in 2012 to 7.3 million in 2025 and is estimated to reach 9.5 million in 2040. With a quarter of the elderly (65 years and older) suffering from dementia, the related social cost is projected to be 21 trillion yen in 2030. The growth rate of the market in neurological therapeutics over the next five years is estimated to be significantly higher than that of the past five years.
Looking at the efforts in some major countries, the U.S. has plans to invest more than $5 billion in the 'BRAIN Initiative' from 2013 to 2025, the EU's 'Human Brain Project' (HBP) expects to budget about 610 million euros over 10 years, and China has a five-year plan, starting in 2021, with a budget of 5 billion yuan. Compared to Japan's efforts, very large investments are being made in the public sector.
However, Japan's private companies lead the world, with the pharmaceutical company 'Eisai,' for example, having developed the first therapeutic drug for Alzheimer-type dementia, Lecanemab, which has been quickly approved by the U.S. Food and Drug Administration (FDA) and is expected to be available globally soon. Japan has one of the largest neurological disease-related pipelines (the set of drug candidates) in the world and is ranked among the world's top countries in this sector.
In the field of brain science research, Japan has been producing remarkable results that will lead to the development of therapeutic drugs through such initiatives as Brain/MINDS (Brain Mapping by Integrated Neurotechnologies for Disease Studies) and Brain/MINDS Beyond (the Strategic International Brain Science Research Promotion Program).
For example, in addition to developing a blueprint for the marmoset brain that connects cells to the whole brain level, Japan has created the world's first disease model marmosets (for Alzheimer's disease, Parkinson's disease, developmental disorders). As a new disease model leading to the clarification of the neural circuits underlying higher functions unique to humans, it will lead to breakthroughs in drug discovery research. The next-generation infrastructure for generating potential treatments and drug discovery for diseases has been established, including a clinical MRI database unrivaled by any other in the world (with thousands of cases, a wide range of disease types) and a brain bank network (postmortem brains). Under the above programs, the world's largest and fastest wide-field two-photon microscope has been devised to enable network analysis at the cellular level of the activity of multiple neurons for the first time in the world, and a probe that can monitor neural activity in the brain of marmosets during free movement. These advances provide new possibilities to pioneer measurement technologies integrating activities at the single-cell and circuit levels with behavior. Furthermore, Japan has succeeded in imaging abnormal proteins (tau and α-synuclein) that cause neurodegenerative diseases in living brains, obtaining non-clinical proof-of-concept for the technology used.
Under the new program, the following research and development (R&D) will be promoted by strengthening collaboration between basic and clinical medicine and by partnerships between academia and industry: furthering the results of innovative technology and research infrastructure to date; gaining deeper insights into brain mechanisms; constructing a research infrastructure for mathematical models (digital brain); and harnessing the R&D potential of groundbreaking technologies for diagnosis, treatment and drug discovery for neurological diseases such as dementia.
More specifically, core organizations will be established, priority research areas will be identified, and research and practical application support teams will be organized.
The program will establish five priority research areas:
(1) Development of potential for the treatment of neuropsychiatric diseases, including identification of target factors for drug discovery based on the structural analysis of degenerated protein molecules; development of new treatment methods focusing on disease-related circuits by leveraging model animals and mathematical models; and the development of simplified biomarkers.
(2) Understanding of the dynamics of higher functions of the human brain, including the generation of interspecies, multidimensional, and multilevel data relevant to dynamics analysis; untangling of neuronal dynamics at the level of molecules, cells and neurocircuits, as well as the clarification of the mechanisms interconnecting cortical and subcortical regions.
(3) Investigation of human pathological mechanisms, including the unraveling of mechanisms of aggregate protein propagation utilizing model animals including disease marmosets; understanding mechanisms related to neural circuit disorders and symptoms; and identification of neural circuits accounting for disruption and the cell types involved.
(4) Development of the digital brain, including reconstruction of the connectome of the human brain in a digital space using mathematical models of model animals, and reconstruction of a predictive model for disease states based on pathological mechanisms, etc.
(5) Provision, development and upgrading of innovative technologies and research infrastructure, including the development of platforms integrating innovative imaging technologies; a human MRI database and marmoset brain database, etc.; supply of marmosets and development of disease marmosets; and development of networks for postmortem brains.
For these priority issues, research projects will be solicited for the following team-type frameworks: a framework encouraging the fusion of different fields and collaboration between basic and clinical fields, a framework for young researchers, a framework for interdisciplinary/exploratory research, and a framework for research collaboration with industry.
The Japanese government puts a lot of effort into dealing with dementia, and on August 25, the Specialist Committee for the Promotion of Health and Medical Care Strategy decided to establish an R&D initiative for dementia and cerebral nerve disease. The Ministry of Health, Labour and Welfare (MHLW) is providing support for R&D that directly links the potential for drug discovery to clinical trials and the establishment of an international joint clinical trial system. The Ministry of Economy, Trade and Industry (METI) underpins the development of relevant medical devices, etc., and the MEXT's project aims to promote research that will enable the discovery of the potential for future drugs and the development of medical devices. The Cabinet Office also set a new Moonshot goal of restoring the lost functions of damaged neurons in the brain.
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.