Neuroscientists, Welcome to Washington!

Friday, November 10, 2017

This week, more than thirty thousand neuroscientists are coming to Washington, DC for the annual meeting of the Society for Neuroscience (SfN). The meeting is the largest scientific conference on brain and nervous system research, and I am looking forward to hearing about the latest science advances, speaking with NINDS grantees, catching up with colleagues and collaborators, and meeting investigators just entering the field. We are a growing field, fueled by heightened public interest, and I always leave the meeting feeling reenergized by the exciting science and individuals I meet.

At NINDS, we rely on this talented community to advance our mission; both researchers to drive the discoveries but also staff to lead and administer our programs. Growing a healthy neuroscience workforce is one of my top priorities. Among my focuses at SfN will be to share news about our new NINDS mentorship award, programs and policies at NINDS and NIH to help researchers balance family and personal needs with busy research careers, and to spread the word about important open positions within our own institute. For those attending the meeting, please come by booth 3404 to learn more.

As I’ve written about recently, NINDS is offering a new mentorship award, named after my predecessor, Dr. Story Landis. Nominations for the inaugural year of this award are due December 15 – please take a moment to consider nominating someone that has been an extraordinary mentor for you. This year, NINDS is seeking nominees for junior faculty members who have demonstrated dedication to training and ensuring that their trainees become exceptional scientists, I know how critical mentoring is, and we are hoping to reward and incentivize excellence in mentoring with the recognition and financial support that come with this award, which includes $100,000 in direct costs for an investigator to use to foster the career advancement for trainees. More information can be found here.

In concert with mentoring, we are working to enhance postdoctoral training by focusing the NINDS postdoctoral fellowship training (F32) on the beginning of the postdoctoral training period. By requiring an applicant to submit an application before the end of their first year in the new lab, and emphasizing the importance of an innovative, impactful project, and rigorous quantitative training, NINDS hopes to spur talented trainees to move successfully to the next phase of their careers more quickly. Indeed, our interest in bold new ideas is so strong that we hope that students will develop an idea with their future mentor before they start their postdoctoral training and apply while finishing up their predoctoral career. With the new NINDS F32, we actually don’t want preliminary data. We want great ideas to do important research. What NINDS does not want is to discourage researchers who have a child during this period from obtaining a fellowship  – extensions of the eligibility window are readily available for the F32 (and other training mechanisms, such as the K99/R00) for parental leave or other well-justified leave. Please reach out to your program director or the NINDS training director to learn more.

We also want the community to be aware that this FOA features new language for fellows who have children during their fellowship. Many early career investigators face a tough balancing act between work in the lab and starting families. Unfortunately, the evidence suggests that having children is a major reason for why young female scientists opt out the academic pipeline before obtaining their first academic research jobs. While addressing this challenge will ultimately require a sustained, multi-pronged approach, as a first step NINDS is encouraging Fellows who have a child during the period of their F32 award and serve as the primary caregiver to request a six-month paid extension of their fellowship. We are considering this a pilot program, and after evaluation, will consider expanding it to other training funding opportunities.

We believe these flexibilities will not only train fellows to be better scientists, but will enable fellows to balance research with new parental responsibility.

The NINDS model for the postdoctoral training fellowship has been adopted by the NIH BRAIN Initiative, which just released a new postdoctoral fellowship opportunity (F32) for fellows who have the potential to become productive investigators in research areas that will advance the goals of the BRAIN Initiative. A special focus in this initiative is encouraging scientists from other fields to collaborate with neuroscientists. We welcome scientists in the fields of statistics, physics, mathematics, engineering, and computer and information sciences to get involved in experimental neuroscience. As with the NINDS fellowship, we are emphasizing the importance of scientific skills and rigor in these applications. As I have stated before, a focus on robust, reproducible results is critical to our mission of understanding the brain and nervous system and reducing the burden of neurological disease. Further, with this fellowship, we are providing the opportunity to support postdoctoral research on the ethical implications of recent advancements in neurotechnology and brain science

Lastly, NINDS is hoping to utilize our robust neuroscience workforce to recruit a few motivated leaders to direct critical programs here in our Institute. We are currently searching for a Director for our newly-established Division of Neuroscience. This individual will lead the largest portfolio in our extramural research program and is critical to charting the future of a vibrant, growing neuroscience research community. From a trans-NIH perspective, we are also looking for an exceptional scientist to lead the NIH BRAIN Initiative, a complex program involving 10 NIH neuroscience Institutes and Center that is aimed at revolutionizing our understanding of the human brain. The NIH BRAIN Initiative Director will lead the innovative trans-NIH component of this collaborative, public-private research initiative and coordinate with the multiple federal and non-federal participants to ensure we collectively meet the initiatives bold, audacious goals. More information on these exciting, high profile positions can be found here.

To learn more about all of these opportunities, please come visit booth 3404 at the meeting or reach out to the NINDS program directors and staff who will be attending. I am excited to meet and interact with many of you and make the neuroscience field the best it can be. 

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Boosting Research on Alzheimer’s Disease and Related Dementias (AD/ADRD)

Monday, October 30, 2017

If you know anyone with dementia, you probably understand how devastating it is to those affected and their families. Alzheimer’s Disease (AD), the most common and widely-diagnosed neurodegenerative disorder, affects more than 5 million people in the United States. Other related forms of dementia also affect millions of Americans and commonly co-occur with typical AD, representing a significant and increasing burden on public health. Known as AD-related dementias (ADRD), these include Lewy body dementia (LBD), frontotemporal dementia (FTD), vascular cognitive impairment/dementia (VCI/D), and mixed dementias. Notably, cerebrovascular disease is exceedingly common in older populations who are diagnosed with AD and in persons with disabling age-related cognitive decline. 

Congressional appropriations to the NIH in Fiscal Years (FY) 2016 and 2017 provided a generous boost in funding for AD and ADRD research – an additional $350 million in FY2016 and an additional $400 million in FY2017. As a lead NIH Institute for research on ADRD, NINDS collaborates with the National Institute on Aging (NIA), the lead NIH Institute for AD research, to put these funds to work by creating new funding opportunity announcements (FOAs) and extending the payline for meritorious investigator-initiated projects on AD/ADRD. Going forward, NINDS and NIA will continue to partner in AD/ADRD research planning and implementation, and we urge the research community to join in our efforts to accelerate scientific progress toward reducing the enormous burden and cost of dementia.

The need for scientific effort to reduce the burden of Alzheimer’s Disease and Related Dementias

Currently, there are no disease-modifying treatments available for AD, LBD, FTD, vascular, and mixed dementias, and the lack of optimal clinical diagnostic tools for dementia makes it even more challenging to find effective treatments or guide patient care. We have previously noted the importance of controlling hypertension, the primary driver of cerebrovascular disease, for stroke prevention and healthy brain aging. A recent report from the National Academies of Sciences, Engineering, and Medicine, “Preventing Cognitive Decline and Dementia: A Way Forward,” concluded that the “evidence suggests that managing blood pressure for people with hypertension, particularly during midlife (ages 35 to 65 years), is supported by encouraging but inconclusive evidence for preventing, delaying, and slowing clinical Alzheimer’s-type dementia.” While promising, we still have much to learn about the interaction between vascular and AD pathology, how to leverage cardio- and cerebro-vascular health measures to prevent dementia, and moreover, how to prevent or halt other types of dementia.

Chart showing the change in NIH Research Funding for AD and ADRD.
Since 2011, the NIH budget for AD/ADRD research has more than doubled. The first largest increase occurred in FY2016, when NIH received an additional $350 million toward AD/ADRD research. (Based on data from the NIH RePORT Categorical Spending). In FY2017, NIH received an additional $400 million (not shown in graph)

As the U.S. population ages, we need to reduce the tremendous health and economic burdens that face individuals with dementia, their loved ones, caregivers, and society. Recognizing this urgent need, Congress passed and President Obama signed the National Alzheimer’s Project Act (NAPA) into law in 2011, as a coordinated national effort to fight AD/ADRD. Since then, the NIH budget for AD/ADRD research has more than doubled, including the significant increase in funds in FY2016 and FY2017. 

Extended Payline for AD/ADRD Investigator-initiated Research

Since FY2016, the NIA has utilized a higher pay line for AD/ADRD research to support investigator-initiated research grants, which it extends to NINDS and other Institutes and Centers for applications that meet this bar. This pay line is considerably higher than the pay line for other types of research in either NINDS or NIA. NINDS remains very interested in grant submissions focused on innovative ideas that could lead to prevention or effective treatment of AD/ADRD. 

Future Opportunities

NINDS is also actively developing concepts for new initiatives to address research priorities identified through periodic NIH-hosted ADRD Summits (ADRD 2013 & ADRD 2016), where researchers, clinicians, patients, caregivers, and advocates gather to assess scientific progress and generate research recommendations. Some of these prioritized scientific opportunities include improving understanding of disease mechanisms in ADRD, determining the presence and significance of co-morbid brain pathologies in individuals with AD/ADRD, and improving clinical detection and diagnoses of AD/ADRD. Last year, the National Advisory Neurological Disorders and Stroke Council (NANDSC), the Advisory Council to NINDS, approved several AD/ADRD research concepts to be further developed into new programs and initiatives as funds become available. Six examples are shown below.

      NINDS’s ADRD research concepts for FY2018

  • Center without Walls (CWOW) for ADRD Radioligand Development and Testing – This would support the development of imaging ligands for Tau, TDP43, synuclein, and synaptic and neuroinflammatory markers that will enable better patient stratification, diagnosis, and tracking of disease progression in FTD ,  LBD  and dementias with mixed etiologies. Current Tau PET ligands, which were identified by screening for binding in AD tissue, lack the specificity and sensitivity required for the tau-related ADRDs. The research focus could include screening of existing and derivative compounds against tau, as well as the other protein aggregates found in FTD, LBD, and Parkinson’s Disease human tissue. The Center could support the synthesis of ligands, analysis of ligands in human tissue, and first-in-human studies. 
  • Planning Grants for Clinical Trials to develop treatments for LBD – To address the lack of treatments for the disabling clinical features of LBD, this concept was developed to provide support to convene a clinical trial team that will develop the rationale and research design required for the submission of an NIH clinical trial grant application.   
  • Mechanisms of diffuse white matter disease and small vessel pathology in Vascular Contributions to Cognitive Impairment and Dementia (VCID) – This would support hypothesis-testing research to elucidate cellular and molecular mechanisms that underlie diffuse white matter disease and small vessel disease in VCID. The ultimate goal is to develop a rigorous mechanistic understanding that will enable future translational and clinical studies in VCI/D, AD, and other mixed etiology dementias that include diffuse white matter disease and small vessel pathology.
  • LBD Center without Walls – A collaborative, multidisciplinary and possibly multi-national research group would be developed to elucidate the neuropathological mechanisms that result in the clinical pathology characteristic of LBD.  The Centers will focus on understanding interactions between tau and alpha-synuclein and how these contribute to selective cell and circuit vulnerabilities.
  • Pathway and target discovery for ADRD – This would support the discovery and validation of new pathways, targets, and potential biomarkers related to the human biology of ADRD, and support hypothesis-driven research using enhanced bioinformatics for large scale data analysis and disease modeling. Researchers would be encouraged to use existing cohorts, data, and well-characterized biological resources.
  • Understanding the structural biology of ADRD-associated proteins – This would leverage recent advances in Cryo-electron microscopy (Cryo-EM) to identify structural forms of ADRD-associated proteins present in human brain tissue.  Understanding structural differences in strains or isoforms of proteins like tau, alpha-synuclein, and TPD43 will support and advance the basic biology underlying ADRD, as well as contribute to the development of better diagnostic tools and therapies for these diseases.

Now is truly an exciting time for dementia research, and our program staff is working hard to transform these concepts into real funding announcements. In the meantime, I strongly encourage the research community to develop ideas and be prepared to take advantage of upcoming, unprecedented opportunities to advance ADRD research. 

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