Neuron
Editorial Bridging the Gap This special issue looks at the challenges associated with translational neuroscience and, more specifically, at the gap between the vision and promise of translational neuroscience and what it has thus far been able to deliver, in terms of new clinical treatments and cures for patients in need. A starting point for most of the pieces in this issue is an overview of the current state of affairs. They paint a dire picture. The impact of brain disorders is on the rise. Neuropsychiatric disorders including autism, schizophrenia, intellectual disability, and epilepsies account for the greatest source of disease burden for young people. At the other end of the spectrum, with longer life spans, neurodegenerative disorders like Alzheimer’s and Parkinson’s are debilitating for the elderly and devastating for their families. Brain injuries and stroke are on the rise. A variety of global impact studies have identified brain disorders as a leading contributor to disabilities and morbidity worldwide with a critical economic, public health, and societal impact. Some have referred to brain disorders as a ‘‘ticking economic bomb.’’ Beyond the economics, the broader societal and human impact can’t be underestimated. Indeed, there are few of us whose lives have not been touched in some way by brain disorders, whether ourselves, directly, or through our family members, colleagues, and friends. While the disease burden and economic impacts are on the rise, progress in the development of new therapeutics and treatment approaches has appeared to have stalled. As pointed out in several perspectives in this issue, approvals for new therapeutics (whether drugs, devices, or other treatment approaches) for nervous system disorders have been declining and most of the treatments we currently have are not disease modifying. Further, despite the clear unmet need and apparently growing potential market, over the last years a number of large pharmaceutical companies have shifted their strategies away from neuroscience. The reasons for this disconnect and for the limited progress are complex and much discussed, both in the scientific literature and in the general press. The drug development process is long, expensive, and risky, now more so than ever, given the poor track record of clinical trials and regulatory approvals for drugs for nervous system disorders. At the same time, despite the doom and gloom prognostics, there are reasons to be optimistic. The pace of research progress in neuroscience over recent years has been nothing short of amazing. At all levels of neuroscience, from molecular to cellular to systems and cognitive neuroscience, we have witnessed an explosion of new tools, approaches, and discoveries. New national and international initiatives focusing on the brain, like BRAIN Initiative in the U.S., the European Human Brain Project, and similar initiatives in Asia and around the globe, are a good sign and offer inspiration for the community. Foundations, philanthropists, and patient groups are playing important roles in bridging the gaps in research funding for basic and applied work and, just as importantly, have stepped forward as platforms for innovation and new ways of thinking. It is also encouraging to start to see some recent signs of a reversing of the trend of industry retreat from neuroscience, in particular with efforts from several major pharmaceutical companies to establish more neuroscience-focused academic-industry partnerships. And there is broad commitment to the cause. Across all stakeholders—industry, academia, government, policymakers and advocates, private philanthropy, patient groups, patients—there is resounding agreement that we need new approaches and strategies and there are active efforts, discussion, and experimentation aimed at making the process of therapeutic development more efficient and effective. As the saying goes, ‘‘Necessity is the mother of invention.’’ Our goals for this special issue are to provide an overview of some of the key challenges for the path from bench to bedside and showcase some of the new approaches that are being taken. We challenged authors not just to speak to the problems but also to offer solutions and ideas for bridging this gap between basic discoveries and clinical applications. It would not be possible to cover all topics of relevance to an issue as multilayered as this one, but we hope that the perspectives and ideas highlighted here will provide ample fodder for discussion and promote a dialog within the community. In selecting authors for this series, we invited those who bring broad expertise and represent the breadth of stakeholders in this space, including academia, industry, policy and government, and philanthropy. This review issue purposefully focuses to the largest degree on the broad strategic and organizational challenges, rather than the scientific challenges for particular diseases. Throughout the pieces in the issue, we highlight examples based on specific diseases, but the aim here is not to cover the disease biology in detail but rather to offer case studies for the broader strategic issues discussed. If you are interested in more translational and disease-related content from Neuron, please check out our Translational Neuroscience Collection (http://www.cell.com/neuron/collections/translational-neuroscience), where we’ve brought together a collection of research articles, reviews, and perspectives on translational neuroscience. A common theme that emerged from many of the pieces in this issue was the call for collaboration and more coordination across sectors and stakeholders. Such collaborations can take a diversity of forms, whether more traditional research collaborations within academia, across disciplines and expertise, as well as between basic and clinical scientists; academic-industry partnerships at different stages of the pipeline; team-based projects and research initiatives to take advantage of scale, along the lines of what one sees in physics or at places like the Allen Institute for Brain Science; consortia to promote sharing of materials and knowledge (a strategy that has been used to great effect in the genetics community); large-scale mission-driven public-private partnerships like the U.S. BRAIN Initiative; or ones that are more focused on a particular disease area, like the EU-AIMS project described in this issue. The common thread is that in leveraging shared resources, tools, and knowledge and approaching these difficult problems collaboratively, we can achieve more together. Of course, this is not to say that collaboration is a panacea. Clearly, tackling these challenges will take more than simply working together and will require new ideas, leadership, and innovation on multiple Neuron 84, November 5, 2014 ª2014 Elsevier Inc. 513
Neuron
Editorial levels: scientific, organizational, and strategic. One area where we can come together is in advocacy, whether this be in engaging policymakers around key policy issues that affect the neuroscience research community (including, but not limited to, funding issues) or in educating the public toward a better understanding of science and neuroscience. The more we can demonstrate to policymakers and the general public that neuroscience research has important social, economic, and public health benefits, the better case we can make for ongoing global investment and support of our research. A few words should also be said about the contribution of basic research to translational neuroscience. Too often, lines are drawn between ‘‘basic,’’ ‘‘translational,’’ and ‘‘clinical.’’ More and more in today’s climate of constrained resources, time, and funding, there is a tendency to see these as separable camps with differing approaches and agendas, competing for the same limited resources in a sort of ‘‘zero-sum game.’’ The reality is more nuanced, symbiotic, and optimistic. There is significant overlap between these domains, in terms of scope and approaches, and also, more and more, the people involved. Moreover, the trajectory from basic research insight to application in a clinical setting is rarely (if ever) a linear progression. More often the path is circular and iterative. Basic research offers stepping stones to clinical applications, but clinical medicine also informs our understanding of basic neurobiology. A strong translational pipeline needs a foundation of strong basic research. To underscore this point, we’d invite you to re-read the perspective that Tom Insel and Story Landis wrote for our Neuron 25th Anniversary issue last year (http://www.cell.com/neuron/ abstract/S0896-6273(13)00898-2) that eloquently makes a case for the importance of basic research and of a deeper understanding of fundamental neurobiology on translational neuroscience. As Landis and Insel wrote, ‘‘We need a deeper understanding of the basic biology of how the brain works in both health and disease. This understanding will require better tools, more basic science, more human neurobiology, and a continued commitment to a diverse workforce funded for innovation.’’ We here at Neuron wholeheartedly agree. We’re enormously grateful to all the authors who contributed to this series. As this collection testifies, there is tremendous excitement and energy around the opportunities before us, despite the many challenges. We hope that these perspectives will stimulate discussion, debate, and engagement. Indeed, we hope to continue the discussion on this important topic for our field in the pages of Neuron and plan to feature perspectives and essays on issues related to translational neuroscience in an ongoing way. We invite you to share your ideas for topics and issues that you’d like to see addressed. Please feel free to email us directly ([email protected]). Our Cell Symposia SFN Satellite meeting (November 13–14) is also on ‘‘Translational Neuroscience: Bridging the Gap between Basic Research Discoveries and Clinical Applications.’’ We are still accepting registrations and late-breaking poster submissions. For additional information, please go to our Cell Symposia page online (http://www.cell-symposia-translationalneuroscience. com). Similar to the perspective taken in this special issue, this symposium will focus on the question of how we can move from the understanding of disease mechanisms toward the translation into therapeutics. Using case studies drawn from different disease areas, we will highlight areas in which progress has been made, consider the roadblocks and how we might overcome them, and, moving beyond the lab, address how policy and organizational issues impact these scientific efforts. The speaker list is outstanding and we hope that you can join us for what is sure to be an exciting and stimulating meeting. In conjunction with this review series and the Cell Symposia, we will also be hosting a series of webinars on issues related to translational neuroscience. The first of these, on biomarkers for neurodegenerative disorders, featuring David Holtzman, Scott Small, and Reisa Sperling, took place on October 30th. You can still view the archived recording at http://view6.workcast.net/register? pak=7621420763042973. In the second of this series of webinars on translational neuroscience, on December 16th, Ricardo Dolmetsch, Kevin Eggan, and Rusty Gage will discuss the potential of groundbreaking pluripotent stem cell technologies to model ‘‘human’’ disease pathology and as platforms for drug development. Stay tuned for more information on this series as well as other exciting webinar offerings at http://www.cell.com/webinars. All webinars are free thanks to the generous support of our sponsors. In closing, we also want to invite you to connect with us at SFN. Neuron and the Cell Press team are excited to be in Washington, DC for SFN. Neuron will be represented at the Cell Press/Elsevier booth (#115). We’ll be showcasing content from across Cell Press. Please stop by and pick up your free copies of our two special SFN issues—this review issue on translational neuroscience and the featured research issue—as well as our annual special collection ‘‘Best of Neuron’’ and the recent review issue on neural connectomics (http://www.cell.com/neuron/issue?pii=S0896-6273(14)X0018-8). You’ll also find copies of other Cell Press journals, including Cell, Cell Reports, Current Biology, Trends in Neurosciences, and Trends in Cognitive Sciences. The Cell Press editors will be hosting ‘‘Meet the Editors’’ events on Sunday, Monday, and Tuesday (Nov. 16–18), so please come by and say hello. http://dx.doi.org/10.1016/j.neuron.2014.10.044
514 Neuron 84, November 5, 2014 ª2014 Elsevier Inc.
Editorial Bridging the Gap This special issue looks at the challenges associated with translational neuroscience and, more specifically, at the gap between the vision and promise of translational neuroscience and what it has thus far been able to deliver, in terms of new clinical treatments and cures for patients in need. A starting point for most of the pieces in this issue is an overview of the current state of affairs. They paint a dire picture. The impact of brain disorders is on the rise. Neuropsychiatric disorders including autism, schizophrenia, intellectual disability, and epilepsies account for the greatest source of disease burden for young people. At the other end of the spectrum, with longer life spans, neurodegenerative disorders like Alzheimer’s and Parkinson’s are debilitating for the elderly and devastating for their families. Brain injuries and stroke are on the rise. A variety of global impact studies have identified brain disorders as a leading contributor to disabilities and morbidity worldwide with a critical economic, public health, and societal impact. Some have referred to brain disorders as a ‘‘ticking economic bomb.’’ Beyond the economics, the broader societal and human impact can’t be underestimated. Indeed, there are few of us whose lives have not been touched in some way by brain disorders, whether ourselves, directly, or through our family members, colleagues, and friends. While the disease burden and economic impacts are on the rise, progress in the development of new therapeutics and treatment approaches has appeared to have stalled. As pointed out in several perspectives in this issue, approvals for new therapeutics (whether drugs, devices, or other treatment approaches) for nervous system disorders have been declining and most of the treatments we currently have are not disease modifying. Further, despite the clear unmet need and apparently growing potential market, over the last years a number of large pharmaceutical companies have shifted their strategies away from neuroscience. The reasons for this disconnect and for the limited progress are complex and much discussed, both in the scientific literature and in the general press. The drug development process is long, expensive, and risky, now more so than ever, given the poor track record of clinical trials and regulatory approvals for drugs for nervous system disorders. At the same time, despite the doom and gloom prognostics, there are reasons to be optimistic. The pace of research progress in neuroscience over recent years has been nothing short of amazing. At all levels of neuroscience, from molecular to cellular to systems and cognitive neuroscience, we have witnessed an explosion of new tools, approaches, and discoveries. New national and international initiatives focusing on the brain, like BRAIN Initiative in the U.S., the European Human Brain Project, and similar initiatives in Asia and around the globe, are a good sign and offer inspiration for the community. Foundations, philanthropists, and patient groups are playing important roles in bridging the gaps in research funding for basic and applied work and, just as importantly, have stepped forward as platforms for innovation and new ways of thinking. It is also encouraging to start to see some recent signs of a reversing of the trend of industry retreat from neuroscience, in particular with efforts from several major pharmaceutical companies to establish more neuroscience-focused academic-industry partnerships. And there is broad commitment to the cause. Across all stakeholders—industry, academia, government, policymakers and advocates, private philanthropy, patient groups, patients—there is resounding agreement that we need new approaches and strategies and there are active efforts, discussion, and experimentation aimed at making the process of therapeutic development more efficient and effective. As the saying goes, ‘‘Necessity is the mother of invention.’’ Our goals for this special issue are to provide an overview of some of the key challenges for the path from bench to bedside and showcase some of the new approaches that are being taken. We challenged authors not just to speak to the problems but also to offer solutions and ideas for bridging this gap between basic discoveries and clinical applications. It would not be possible to cover all topics of relevance to an issue as multilayered as this one, but we hope that the perspectives and ideas highlighted here will provide ample fodder for discussion and promote a dialog within the community. In selecting authors for this series, we invited those who bring broad expertise and represent the breadth of stakeholders in this space, including academia, industry, policy and government, and philanthropy. This review issue purposefully focuses to the largest degree on the broad strategic and organizational challenges, rather than the scientific challenges for particular diseases. Throughout the pieces in the issue, we highlight examples based on specific diseases, but the aim here is not to cover the disease biology in detail but rather to offer case studies for the broader strategic issues discussed. If you are interested in more translational and disease-related content from Neuron, please check out our Translational Neuroscience Collection (http://www.cell.com/neuron/collections/translational-neuroscience), where we’ve brought together a collection of research articles, reviews, and perspectives on translational neuroscience. A common theme that emerged from many of the pieces in this issue was the call for collaboration and more coordination across sectors and stakeholders. Such collaborations can take a diversity of forms, whether more traditional research collaborations within academia, across disciplines and expertise, as well as between basic and clinical scientists; academic-industry partnerships at different stages of the pipeline; team-based projects and research initiatives to take advantage of scale, along the lines of what one sees in physics or at places like the Allen Institute for Brain Science; consortia to promote sharing of materials and knowledge (a strategy that has been used to great effect in the genetics community); large-scale mission-driven public-private partnerships like the U.S. BRAIN Initiative; or ones that are more focused on a particular disease area, like the EU-AIMS project described in this issue. The common thread is that in leveraging shared resources, tools, and knowledge and approaching these difficult problems collaboratively, we can achieve more together. Of course, this is not to say that collaboration is a panacea. Clearly, tackling these challenges will take more than simply working together and will require new ideas, leadership, and innovation on multiple Neuron 84, November 5, 2014 ª2014 Elsevier Inc. 513
Neuron
Editorial levels: scientific, organizational, and strategic. One area where we can come together is in advocacy, whether this be in engaging policymakers around key policy issues that affect the neuroscience research community (including, but not limited to, funding issues) or in educating the public toward a better understanding of science and neuroscience. The more we can demonstrate to policymakers and the general public that neuroscience research has important social, economic, and public health benefits, the better case we can make for ongoing global investment and support of our research. A few words should also be said about the contribution of basic research to translational neuroscience. Too often, lines are drawn between ‘‘basic,’’ ‘‘translational,’’ and ‘‘clinical.’’ More and more in today’s climate of constrained resources, time, and funding, there is a tendency to see these as separable camps with differing approaches and agendas, competing for the same limited resources in a sort of ‘‘zero-sum game.’’ The reality is more nuanced, symbiotic, and optimistic. There is significant overlap between these domains, in terms of scope and approaches, and also, more and more, the people involved. Moreover, the trajectory from basic research insight to application in a clinical setting is rarely (if ever) a linear progression. More often the path is circular and iterative. Basic research offers stepping stones to clinical applications, but clinical medicine also informs our understanding of basic neurobiology. A strong translational pipeline needs a foundation of strong basic research. To underscore this point, we’d invite you to re-read the perspective that Tom Insel and Story Landis wrote for our Neuron 25th Anniversary issue last year (http://www.cell.com/neuron/ abstract/S0896-6273(13)00898-2) that eloquently makes a case for the importance of basic research and of a deeper understanding of fundamental neurobiology on translational neuroscience. As Landis and Insel wrote, ‘‘We need a deeper understanding of the basic biology of how the brain works in both health and disease. This understanding will require better tools, more basic science, more human neurobiology, and a continued commitment to a diverse workforce funded for innovation.’’ We here at Neuron wholeheartedly agree. We’re enormously grateful to all the authors who contributed to this series. As this collection testifies, there is tremendous excitement and energy around the opportunities before us, despite the many challenges. We hope that these perspectives will stimulate discussion, debate, and engagement. Indeed, we hope to continue the discussion on this important topic for our field in the pages of Neuron and plan to feature perspectives and essays on issues related to translational neuroscience in an ongoing way. We invite you to share your ideas for topics and issues that you’d like to see addressed. Please feel free to email us directly ([email protected]). Our Cell Symposia SFN Satellite meeting (November 13–14) is also on ‘‘Translational Neuroscience: Bridging the Gap between Basic Research Discoveries and Clinical Applications.’’ We are still accepting registrations and late-breaking poster submissions. For additional information, please go to our Cell Symposia page online (http://www.cell-symposia-translationalneuroscience. com). Similar to the perspective taken in this special issue, this symposium will focus on the question of how we can move from the understanding of disease mechanisms toward the translation into therapeutics. Using case studies drawn from different disease areas, we will highlight areas in which progress has been made, consider the roadblocks and how we might overcome them, and, moving beyond the lab, address how policy and organizational issues impact these scientific efforts. The speaker list is outstanding and we hope that you can join us for what is sure to be an exciting and stimulating meeting. In conjunction with this review series and the Cell Symposia, we will also be hosting a series of webinars on issues related to translational neuroscience. The first of these, on biomarkers for neurodegenerative disorders, featuring David Holtzman, Scott Small, and Reisa Sperling, took place on October 30th. You can still view the archived recording at http://view6.workcast.net/register? pak=7621420763042973. In the second of this series of webinars on translational neuroscience, on December 16th, Ricardo Dolmetsch, Kevin Eggan, and Rusty Gage will discuss the potential of groundbreaking pluripotent stem cell technologies to model ‘‘human’’ disease pathology and as platforms for drug development. Stay tuned for more information on this series as well as other exciting webinar offerings at http://www.cell.com/webinars. All webinars are free thanks to the generous support of our sponsors. In closing, we also want to invite you to connect with us at SFN. Neuron and the Cell Press team are excited to be in Washington, DC for SFN. Neuron will be represented at the Cell Press/Elsevier booth (#115). We’ll be showcasing content from across Cell Press. Please stop by and pick up your free copies of our two special SFN issues—this review issue on translational neuroscience and the featured research issue—as well as our annual special collection ‘‘Best of Neuron’’ and the recent review issue on neural connectomics (http://www.cell.com/neuron/issue?pii=S0896-6273(14)X0018-8). You’ll also find copies of other Cell Press journals, including Cell, Cell Reports, Current Biology, Trends in Neurosciences, and Trends in Cognitive Sciences. The Cell Press editors will be hosting ‘‘Meet the Editors’’ events on Sunday, Monday, and Tuesday (Nov. 16–18), so please come by and say hello. http://dx.doi.org/10.1016/j.neuron.2014.10.044
514 Neuron 84, November 5, 2014 ª2014 Elsevier Inc.
