Special Issue on Disease: Translational Approaches

Abstract

In this issue of Neuron, we are proud to present the first in a series of special issues on neurological and neuropsychiatric disease. The three consecutively published issues will each center around a specific disease-related topic and feature a mixture of Reviews, Perspectives, and NeuroViews. Given the multifaceted nature of the disease field, we chose three themes to allow us to delve into the complexity and diversity of the selected areas. We narrowed the topics to translational approaches to neuroscience, mechanisms of disease, and advances in psychiatry. These topics exemplify the coordinated effort that is required to understand neural mechanisms at different levels to ultimately treat and cure disease. The articles discuss long-standing questions, recent advances, and future directions in this quickly developing sphere. Throughout the series, some diseases and approaches will be covered more than once, but in different contexts, reflecting the interdisciplinary nature of these endeavors In our first special issue, we focus on translational neuroscience, the process of applying insights from laboratory research to the development of clinical trials. It is a rapidly growing discipline in biomedical research and promises to expedite the discovery of new diagnostic tools and drug development as well as unconventional treatment strategies. This collection of pieces helps highlight the themes trending in preclinical to clinical work: gene therapy, advanced biomarkers, and new ways to approach disease research design. We believe that the issue will be of interest to a broad range of scientists, in both research and clinical practice. The first Perspective, by Irene Tracey, Clifford Woolf, and Nick Andrews, discusses pain biomarkers and their importance for the assessment and treatment of pathological pain. Given that pain is a qualitative sensory experience, the authors argue that quantifying pain via a variety of biomarkers is essential for an improved understanding of the disease. The next two Reviews focus on two progressive and devastating neurodegenerative diseases: Huntington disease (HD) and Alzheimer’s disease (AD). In the first piece, clinician-scientists Sarah Tabrizi, Rhia Ghosh, and Blair Leavitt discuss the cutting edge of HD therapeutics. They review approaches to reduce mutant huntingtin protein by targeting huntingtin DNA, RNA, and the mutant protein itself, with the potential to ameliorate all its downstream pathogenic effects. It is an exciting time in this field, as clinical trials in patients are already underway. In their Review of AD, Michaël Belloy, Valerio Napolioni, and Michael Greicius explore ApoE4, a risk factor for AD, among other diseases. By focusing on human data, the authors discuss whether ApoE4 increases the risk for AD via a loss or gain of function. They argue that answering this question is crucial for the development of efficient gene-based therapies for AD. A comprehensive Review by Eloise Hudry and Luk Vandenberghe focuses on the utility of adeno-associated viral vector (AAV) in clinical gene transfer. The article both is a primer on the underlying biology and technologies involved and covers potential applications and trials in the clinic. Indeed, initial clinical successes point to AAV as the most promising avenue for gene therapy development. In their NeuroView, John Krystal, Chadi Abdallah, Gerard Sanacora, Dennis Charney, and Ronald Duman discuss ketamine as a new antidepressant. The discovery of the therapeutically useful, fast-acting antidepressant effects of ketamine is promising and of public health importance. The authors review the discovery of its therapeutic potential, the efforts to develop ketamine as a treatment, and the potential implications for effective pharmacotherapies for depression. The NeuroView by Charles Sanislow, Michele Ferrante, Jennifer Pacheco, Matthew Rudorfer, and Sarah Morris is a useful resource describing the goal and applications of the NIMH Research Domain Criteria (RDoC) and how these approaches can be combined with computational methods to speed advances in translational neuroscience research. We are grateful for the efforts of all the authors in this series and also the reviewers who provided feedback on the articles. We hope we were able to capture the recent developments and promise of the world of bench-to-bedside neuroscience research. These exciting articles highlight how much progress has been made and what lies ahead for the future. Stay tuned for the equally enlightening second and third special issues, focusing on mechanisms of disease and new advances in psychiatry.