Over the past year, we at NINDS have celebrated many great successes in neuroscience. We awarded the first wave of grants for The BRAIN InitiativeSM to over 100 investigators, and new funding opportunities to fulfill the cross-disciplinary goals of BRAIN have been issued with more to come in 2015. The Nobel Assembly presented the Nobel Prize in Physiology or Medicine to neuroscientists for their discoveries of the neurons responsible for processing the brain’s positioning system. Perhaps most exciting of all, in 2014 NINDS-sponsored investigators published over 7,500 peer-reviewed scientific articles ranging from studies that push the boundaries of fundamental knowledge of the nervous system to translational studies that apply basic research concepts to studies that advance clinical diagnostics and treatments to reduce the burden of neurological disease.
Truly, 2014 yielded many exciting moments for neuroscience and we could never summarize them all in a single blog post. What follows are a handful of examples of the stellar research being conducted by NINDS-funded investigators working here on the NIH campus or in universities and research institutions across the country and world. We encourage you to learn more about the amazing discoveries uncovered by NINDS scientists in 2014 by visiting our news pages, reviewing messages and blog posts from the NINDS Director, and exploring the details of our myriad research programs.
Click an image below to access a slide show of NINDS-funded research discoveries in 2014.
NINDS: A look back at 2014
Linking Mechanisms of Synaptic Plasticity to Memory Formation
Targeted Reduction of Huntington Disease Gene to Reduce Disease
Tubulin Acetyltransferase Acts as a Molecular Timer
Tempering Brain Injury with Transcranial Administration of Antioxidants
Selective Stimulation to Promote Functional Recovery in Stroke
Sleep After Learning Enables Neuronal Reactivation and Spine Formation
Neuronal Activity Increases Myelin Formation and Improves Motor
Factors in the Blood of the Young Could Reduce Age-related Decline
In September, NINDS issued awards for the creation of a new center to research sudden unexpected death in epilepsy (SUDEP), the sudden and premature death of a person with epilepsy without apparent or known cause of death. SUDEP is the most common cause of premature mortality in human epilepsy. Unlike many NIH center programs, the Center for SUDEP Research will not be confined to a single institution. This unique consortium is the second of NINDS’s Epilepsy “Centers without Walls” (CWOW), which is a program designed to bring together the best expertise from across U.S. and international institutions to address a challenging research problem for people with epilepsy. The Center for SUDEP Research includes dozens of scientists who are armed with the basic science, computational, genetic, and clinical tools necessary to better understand and develop interventions to prevent this devastating consequence of living with epilepsy.
Evidence suggests that SUDEP may be caused by seizures that induce structural defects and/or brain circuit malfunction in brain stem areas (highlighted in pink) that control cardiovascular and/or respiratory functions. Credit: Patrick J. Lynch, variation by User: Hk kng [CC-BY_SA-3.0] , via Wikimedia Commons
While the causes of SUDEP are currently unclear, mounting evidence points to seizures that induce structural defects and/or brain circuit malfunction in areas that control cardiovascular and/or respiratory functions. Using a multidisciplinary approach, scientists and clinicians participating in the new center without walls hope to understand what causes SUDEP and how can it be prevented.
One team of researchers will identify genes, predisposition to neurochemical imbalances, and structural irregularities in the brain that may increase the risk of cardiac arrhythmias and respiratory disruptions in epilepsy. In parallel, another team will develop a sophisticated repository for storing and sharing genetic, tissue and clinical data samples collected from 400 study participants with epilepsy per year for three years at each of 10 clinical sites across the country. This team will also analyze the collected samples to identify risk factors for SUDEP. More…
Last month the 1,000th subject was enrolled in the Parkinson’s Disease Biomarkers Program (PDBP), marking a major milestone in the efforts of NINDS to develop a method to predict the early onset—and track the progression—of this debilitating neurological disorder.
We have made considerable progress in developing treatments, but people with Parkinson’s still suffer. While current treatments are most effective at alleviating early symptoms of the disease, symptoms in later stages are less responsive, and no intervention has been found to slow disease progression or prevent it. Like many neurological diseases, the search for better Parkinson’s treatments has been hindered by the fact that symptoms—including uncontrollable shaking, rigidity, and impaired balance—only start appearing well after the disease has begun to cause significant changes in the brain. More…
New treatments for the hundreds of disorders that affect the brain are too few and far between. One reason for this lack of treatments is that we do not yet understand how the brain and nervous system work at a fundamental level (see our recent blog post about the need to support basic science). In addition, when potential treatments for nervous system disorders are discovered in the laboratory, researchers in academia often lack the expertise and access to critical infrastructure required to develop a new drug, biologic agent, or device to the point where the biotech/pharma industry will pursue it further. Compounding the problem, and reflected in statistics for pharmaceutical development, is that treatments for brain disorders have particularly long clinical development and approval times (8.8 years) and a low clinical approval success rate (~8%). With such deep risks in terms of time and money, pharma has dialed back early-stage investments in drug development for neurological diseases, despite the large number of people affected who urgently need new and better treatments. Taken together, these factors mean that the clinical application of many promising potential therapies is never fully explored.
NINDS has supported researchers through the discovery and preclinical phases of therapeutic development with several research funding mechanisms, including those developed by the Institute’s Office of Translational Research (OTR). Recognizing the need to play a bigger role in bridging the gap between the discovery of a potential therapy and its development and clinical testing, NINDS staff thoroughly assessed the strengths and weaknesses of our existing programs. Based on that assessment and in consultation with the community, NINDS has just launched three carefully crafted funding programs, each tailored to specific treatment modalities—the Blueprint Neurotherapeutics Network for small molecules, CREATE (Cooperative Research to Enable and Advance Translational Enterprises) Bio, and CREATE Devices. These new milestone-driven programs offer support for preclinical development and potentially small clinical trials and allow researchers in academia and small companies the opportunity to play a more active part in translating their basic neuroscience discoveries into treatments. We hope novel therapies advanced through these programs will become attractive enough to hand off to biotech/pharma companies, which can then lead later-stage development and testing and ultimately produce treatments approved for use in humans. More…
NINDS supports a broad range of research projects, from basic studies of the nervous system to large Phase III clinical trials. Several years ago, we embarked on an institute-wide planning process to analyze and optimize our investments in basic, translational, and clinical research. Triggered by the observation that between 2003 and 2008, NINDS funding for R01s decreased by 10%, we extended our analyses to determine how our extramural funds are distributed across the spectrum of basic and applied research, and whether that distribution has changed over time.
To perform the analysis, we developed simple definitions of basic and applied research (listed at the end of this post) that could be applied as unambiguously and reproducibly as possible. We also divided each of these broad categories into two subcategories—basic/basic, basic/disease-focused, applied/translational, and applied/clinical. Expert neuroscientists, including program directors, scientific review officers, and other members of our staff then assigned funded projects to these subcategories based on careful reading of abstracts, specific aims, and, when necessary, additional sections of the grant application. Because a single application often proposed research in more than one subcategory, we assigned percentages of a grant to each subcategory as appropriate; for example, a grant could be described as 75% basic/basic and 25% basic/disease-focused.
Our analysis covered the period between 1997 and 2012 to ensure that any trends we observed did not reflect a short-term response to a particularly good or bad funding year. This analysis included most of the new and competing continuation grants issued each year. The specific funding mechanisms that we included are described below. Since this was an extremely labor-intensive task (and our staff have day jobs!), we selected eight years within this period for review.
Our first finding was that between 1997 and 2012, NINDS expenditures on applied research as a fraction of total competing research budget increased from 13% to 29% while the proportion of basic research declined from 87% to 71% (Figure 1). Continue reading…