基礎臨床統合シンポジウム（日本神経科学学会将来計画委員会・臨床連携WG合同企画）「基礎・臨床連携の推進に向けて：現状の課題と今後の展望」 Integrated Symposium of Basic and Clinical Neurosciences: Challenges and perspectives to promote integration of basic and clinical neuroscience
S2-5-3-1 精神疾患研究における臨床研究と動物モデル研究の融合の課題 Challenges in integration of clinical and animal model research of mental disorders ○加藤忠史1 ○Tadafumi Kato1 理化学研究所脳科学総合研究センター1 RIKEN Brain Science Institute1 Mental disorders impose severe social burden. Its diagnosis is, however, solely relying on clinical interviews. Currently available drugs have side effects and are not perfect, and thus there are urgent needs to elucidate the causes of mental disorders and develop new diagnostic tests and fundamental treatments. In order to elucidate the causes of mental disorders to develop new treatment and diagnostic methods, we should identify causative mutations at first, and generate animal models that satisfy three validity criteria. Next, its neuropathological basis should be identified. This should be verified in postmortem brains of patients. The disease should be finally defined by neuropathology. In vivo neuroimaging methods to identify such neuropathology should be developed. Fundamental treatment should be developed using animal models, and clinical trials of new drugs should be done based on the defined disease entity, using the developed diagnostic methods. To realize this roadmap, integration of clinical and basic researches is crucial. Though there is concern whether or not mental disorders really exist in animals, it would be possible to model the neural circuit dysfunction causing mental disorders.	S2-5-3-2 神経変性疾患における動物モデルから臨床試験への展開 From animal study to clinical trial of neurodegenerative disease ○勝野雅央1 ○Masahisa Katsuno1 名古屋大学神経内科1 Dept Neurology, Nagoya University1 Neurodegenerative diseases are a group of disorders that affect a certain population of neurons, and are characterized by adult-onset and progressive impairment of cognitive and/or motor function. Recent studies using animal models have given insight into the molecular pathogenesis of neurodegenerative diseases and the development of disease-modifying therapies that slow neurodegeneration. Particularly, transgenic mouse models of autosomal dominant genetic disorders recapitulate certain aspects of molecular pathogenesis in human, and have thus been used for the evaluation of both pharmacological and non-pharmacological therapies. However, the efficacy of these disease-modifying therapies has not been clearly shown in clinical trials. This discrepancy is, at least partially, due to the possibility that the insights obtained from transgenic animals are not necessarily applicable to the sporadic forms of the diseases, which are usually more numerable. For successful translational research on neurodegenerative disorders, several challenges in basic and clinical studies should be overcome. Creation of animal models that faithfully replicate human pathology are fundamental to basic studies, while the implementation of guidelines for pre-clinical research will hopefully increase the chances of success in translational research on molecular-targeted therapies. Utilization of species-independent outcome measures in pre-clinical studies is another key to bridging the gap between basic and clinical research. On the other hand, the efficiency of clinical trials needs to be improved by establishing sensitive, valid biomarkers, enriching the target patient population, and innovative study designs. Initiation of therapy at a pre-symptomatic or early stage is also necessary to assess the efficacy of disease-modifying therapies for neurodegenerative diseases.
S2-5-3-3 iPS細胞のトランスレーショナルリサーチの現状と課題 Current situation and challenges in the translational research using iPS cells ○高橋政代1 ○Masayo Takahashi1 理化学研究所発生・再生科学総合研究センター1 Lab Retinal Regeneration, Center Developmental Biology, RIKEN, Kobe1 Induced pluripotent stem (iPS) cells are an innovative technology and expected to be used as an unlimited source for cell therapies, a tool for drug development and also an ideal material to understand diseases. We have established a culture method that induces directed differentiation of human ES/iPS cells into mature retinal cells. Especially retinal pigment epithelial (RPE) cells can be purified by their colors that means the risk of tumorization from iPS cell remnant will be reduced. RPE cells derived from iPS cells of patients suffering from age-related macular degeneration will be a good candidate for the cell source of transplantation, since they are supposed to avoid the immune rejection. We have prepared the SOP and protocol for a clinical study of these cells. On the other hand photoreceptor cells derived from iPS cells of retinitis pigmentosa patients will be worth investigating the individual mechanism of photoreceptor cell death and evaluating drugs for cell rescue. It is important to make clear strategy and timetables for the translational research. By making a timetable we can find the obstacles toward the goal and prepare for them beforehand. As for the iPS cells there are many obstacles not only technical issues but also political and regulatory matters. However, with many peoples' hope and expectation for the new treatment of incurable diseases, the iPS cell research is now almost reaching the clinical phase.	S2-5-3-4 非侵襲的脳画像とニューロフィードバック Non-invasive neuroimaging and neurofeedback ○橋本龍一郎1 ○Ryuichiro Hashimoto1 首都大学東京人文科学研究科言語科学教室1 Dept Language Sciences, Tokyo Metropolitan University, Tokyo1 Through a series of conceptual and technological innovations over the last decades, the non-invasive functional magnetic resonance imaging (fMRI) has been continuing to open up fruitful research interaction between basic and clinical neurosciences. Conceptual innovations include findings of intrinsic brain activity and its underlying large-scale brain connectivity, which has not only revolutionized our understandings of brain organization, but also shed new light on etiology of several psychiatric diseases. Technological innovations include the development of sophisticated analysis methods that has enabled decoding of contents of information including subjective mental states represented over the distributed regions of the brain. Moreover, increasing computational power in analysis environment has enabled real-time processing of the ongoing signals, which further transformed the fMRI as a powerful tool for neurofeedback, an innovative approach that aims to non-invasively induce brain activity changes for better behavioral outcomes in learning and clinical therapy. In this talk, I review previous applications of neurofeedback for psychiatric conditions and then discuss promises of real-time neurofeedback as a novel research methodology in psychiatry. Previous applications include EEG-based neurofeedback for the treatment of attention-deficit/hyperactivity disorder, and fMRI-based attempts to mitigate clinical symptoms of chronic pain and depression by manipulating activation level of pre-specified regions of interest. Lastly, I will illustrate our research plan of applying the real-time fMRI-based neurofeedback method to create a novel intervention for autism spectrum disorder (ASD) and discuss how recent key innovations in the fMRI literature such as brain decoding and network connectivity analysis can be mobilized into the development of the new methodology.
S2-5-3-5 ヒトにおける侵襲的研究の課題と展望 Invasive Clinical and Basical research in Humans ○貴島晴彦1, 平田正幸1, 柳澤琢史1, 森脇崇1不二門尚2, 吉峰俊樹1 ○Haruhiko Kishima1, Masayuki Hirata1, Takufumi Yanagisawa1, Takashi Moriwaki1, Morris Shayne1, Takashi Fujikado2, Toshiki Yoshimine1 大阪大学医学系研究科脳神経外科1, 大阪大学感覚機能形成学教室2 Department of Neurosurgery, Osaka University Graduate School of Medicine1, Applied Visual Science, Osaka University Graduate School of Medicine2 Biological research has been clasiffied into in vitro, in vivo, and ex vivo, etc forms of research. In accordance with developments in this field in recent years, more emphasis is being placed on the social aspects of research on humans. Various guidelines have been developed in all the areas of medical treatment research, such as those related to the introduction of new medications. However, the application of new and unprecedented technologies into human subjects requires prudent examination and investgation prior to its introduction, such as is the case with regenerative medicine. The field of neuroscience is also no exception. Research involving cytological methods, molecular methods, laboratory animals, and disease modeling with animals has been used in the past, and research on humans has mostly involved non-invasive studies for diagnosis, observational studies, and methods aimed at the medical treatment of the candidate. However, research into systems of human intention, cognition, and sensory functions in the brain are now required, and may need a different approach. With this in mind, possible subjects for neuroscience research in humans are 1) patients with diseases requiring medical treatment, 2) patients with diseases not necessarily requiring medical treatment (patient volunteers), and 3) healthy volunteers. Methods of research in the neurosurgical field include imaging, such as MRI and nuclear imaging, and various methods of peripheral stimulation, which are considered to be forms of non-invasive research. On the other hand, surgical interventions are regarded as invasive types of research, but this classification is not always fair. Future neuroscience research in humans will need to take into account all of the above mentioned topics and methods. Recently, intracranial electrodes and implanted devices are used in patients with neurological diseases for the purpose of treatment and clinical examination. These techniques are also applicable to neuroscience research and aid in the development of therapies. Here, we present our experiences and consider the importance and future of neuroscience studies in humans.	S2-5-3-6 生命倫理およびガバナンスの立場から From standpoints of bioethics and governance ○菱山豊1 ○Yutaka Hishiyama1 文部科学省1 Ministry of Education, Culture, Sports, Science and Technology1 指定発言

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