NINDS Advisory Council Meeting Minutes, September 15-16, 2005

1. Call to Order and Opening Remarks
2. Report of the Director, Division of Extramural Research
3. Report of the Director, NINDS
4. Fiscal Year 2006 Budget Discussion
5. Report of the Director, National Human Genome Research Institute
6. Council Subcommittee Reports
7. Concept Approval for Fiscal Year 2007 Proposed Initiatives
8. Council/Staff Working Group Update
9. NINDS Office of International Activities
10. Council Review of Pending Applications
11. Adjournment

DEPARTMENT OF HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NATIONAL INSTITUTES OF HEALTH
NATIONAL ADVISORY NEUROLOGICAL DISORDERS AND STROKE COUNCIL

Summary of Meeting ¹
September 15-16, 2005

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 164th meeting on September 15-16, 2005, at Building 31, Conference Room 6, Bethesda, Maryland. Dr. Story Landis, Director of the National Institute of Neurological Disorders and Stroke (NINDS), served as Chairperson.

In accordance with Public Law 92-463, the meeting was:

Open: September 15, 2005 - 10:35 a.m. to 5:15 p.m.

for the review and discussion of program development, needs, and policy; and

Closed: September 16, 2005 - 8:00 a.m. to 10:20 a.m.

for the consideration of individual grant applications.

Council members present were:

Mr. Ronald Bartek
Ms. Prisca Chen Marvin (9/15 only)
Dr. Bruce Bean
Dr. Helen Mayberg
Mr. Robi Blumenstein
Dr. Laura Ment
Dr. Raymond Dingledine
Dr. William Mobley
Dr. J. Donald Easton
Dr. David Van Essen
Dr. Francisco Gonzalez-Scarano
Mr. Robert Waterman
Dr. John Loeser
Dr. Huda Zoghbi
Mr. Jeffrey Martin

Council Roster (Attachment 1)

Council members absent were:

Dr. Alicia Conill (participated via teleconference on 9/15)

Ex Officio Member present:

Dr. Paul Hoffman, Department of Veterans Affairs

Ex Officio Member absent:

Dr. Geoffrey Ling, Department of Defense

Members of the public present for portions of the open meeting included:

Dr. Douglas DeWitt, University of Texas Medical Center
Mr. Christian Keller, West Virginia University
Mr. Gene Russo, Research Policy Alert
Ms. Andrea DeSanti, Fisher Bio-Services
Dr. Stephen Korn, University of Connecticut
Ms. Michelle Rodrigues, SRI
Ms. Ann Covalt

NINDS employees present for portions of the meeting included:

Dr. Alan Willard Ms. Ruth Linn Dr. John Marler Dr. Scott Janis Dr. Barbara Radziszewska Dr. Frances Yee Dr. Merrill Mitler Dr. Claudia Moy Dr. Robin Conwit Mr. Michael Loewe Dr. Melinda Kelley Dr. Raul Saavedra Dr. Katrina Gwinn-Hardy Ms. Nena Wells Dr. Story Landis Dr. Brandy Fureman Dr. Linda Porter Ms. Marian Emr Dr. Dan Tagle Dr. Tom Jacobs Dr. Yuan Liu Dr. Alfred Gordon Dr. Emmeline Edwards Dr. Ernie Lyons Dr. Eugene Oliver Dr. Diane Murphy Ms. Quandra Scudder Dr. Laura Mamounas Dr. Robert Baughman Dr. Robert Finkelstein Ms. Stephanie Clipper Ms. Stephanie Fertig Dr. Ursula Utz Ms. Michelle Johnson Dr. Jonathan Horsford Dr. John Porter Dr. Jill Heemskerk Dr. David Owens Dr. Heather Rieff Mr. George Bramhall Ms. Rebecca Desrocher Dr. Wendy Galpern Ms. Margo Warren Ms. Pam Myers Ms. Natalie Frazin Dr. Lauren Murphree Ms. Carol Rowan

Ms. Margaret Jacobs Dr. Andrea Sawczuk Dr. JoAnn McConnell Dr. David Jett Dr. Michael Nunn Dr. Thomas Miller Dr. Naomi Kleitman Dr. Audrey Penn Dr. Yejun He Ms. Maureen Hambrecht Dr. Daofen Chen Dr. Paul Scott Dr. Gabrielle LeBlanc Mr. Paul Myers Dr. Richard Crosland Dr. Randall Stewart Ms. Cikena Reid Ms. Lynn Morin Dr. Robert Zalutsky Dr. Katie Woodbury-Harris Dr. Debra Hirtz Dr. Shanta Rajaram Ms. Rebecca Farkas Ms. Stacey Chambers Dr. Richard Benson Ms. Lynn Rundhaugen Ms. Nancy Hart Mr. Paul Girolami Ms. Shannon Garnett Dr. Audrey Kalehua Dr. Ray Chaudhuri Dr. Shai Silberberg Dr. Ned Talley Mr. Jim Stables Dr. James Coulombe Dr. Joe Pancrazio Ms. Roxane Kerr Dr. Laurie Gutmann Ms. Janice Cordell Ms. Joanne Odenkirchen Mr. Peter Gilbert Mr. Phil Wiethorn Ms. Holly Campbell Rosen Dr. John Lynch Dr. Michelle Jones-London Dr. Mark Scheideler Dr. Robert Riddle

Other Federal employees present for portions of the meeting included:

Dr. Kai Kamerow, NIA
Dr. Kathy Michels, FIC
Dr. Ken Bridbord, FIC
Dr. Toby Behar, CSR
Dr. William Benzing, CSR
Dr. Rene Etcheberrigaray, CSR

I. Call to Order and Opening Remarks

Dr. Robert Finkelstein, Director, Division of Extramural Research, called the meeting to order by introducing himself to new members and apologizing on behalf of Dr. Story Landis who was unable to open the meeting herself. He introduced three new council members: 1) Mr. Robi Blumenstein, President, MRSSI, Inc., which provides consulting and grant-making services to foundations involved in researching Huntington's disease, and a member of Board of Trustees for the League of the Hard of Hearing. 2) Dr. Helen Mayberg, a neurologist and Professor of Psychiatry at Emory. She has an adjunct appointment with the University of Toronto and her research focus is on moods and emotion in health and disease. 3) Dr. Laura Ment is currently a Professor of Neurology in Pediatrics at Yale School of Medicine and studies the influence of preterm birth on brain development.

NINDS periodically invites, as guests of the Council, the chairpersons of review committees and study sections as part of the Institute's continuing effort to strengthen the liaison between initial review groups and the Council. Dr. Finkelstein introduced Dr. Douglas DeWitt, who is Chair of the Clinical Neuroscience and Disease Study Section in CSR. Dr. DeWitt is Professor and Director, Department of Anesthesiology, University of Texas Medical Branch. Dr. Finkelstein also mentioned Council members who were unable to attend this session.

NIH Response to Katrina He then discussed briefly both the NIH and NINDS efforts to assist the victims of Katrina. The first response at the NIH level was the deployment of a medical team. In terms of extramural investments, the Director, Office of Extramural Research, has issued announcements related to application deadlines and possible supplement programs for the future. NINDS staff have also heard that many principal investigators and institutions outside the affected region are willing to host those affected and displaced. NIH is organizing a centralized list of those willing to help. At the NINDS level, a list has been compiled of who has been affected by Katrina, and we are beginning an assessment of how to best remedy each of their problems. One option being considered is a supplement program for people who need money to get their research up and going again, but we don't know how many are affected and what the specific needs will be.

In a discussion relating to Council thoughts on NINDS' response to the victims of Hurricane Katrina, Dr. Zoghbi suggested that perhaps NINDS could organize a list of resources that the community could make available to victims, such as animal models etc. Dr. Finkelstein agreed that this would be a valuable resource and suggested we consider ways to do this. Since it was still early in the recovery process we need to determine what has been lost.

II. Report of the Director, Division of Extramural Research, NINDS

Government in the Sunshine Act and the Federal Advisory Committee Act

Dr. Robert Finkelstein, Director, Division of Extramural Research, reviewed the Government in the Sunshine Act and the Federal Advisory Committee Act, which require the Department of Health and Human Services to open to public observation as many advisory committee meetings as possible, including the National Advisory Councils. The NANDS Council meeting was open to the public, except during the review of grant applications. Notice of the date and place for the Council meeting was published in the Federal Register 30 days prior to the meeting.

Conflict of Interest The regulations concerning conflict of interest were reviewed. Council members were reminded that materials furnished for review purposes and discussion during the closed portions of the meeting are considered privileged information. All Council members present signed a statement certifying that they had not been involved in any conflict of interest situations during the review of grant applications. Council members were also reminded that they need to remove themselves from discussions of applications from any institution from which they have received an honorarium for one year from the time the honorarium was received. If the Council member's participation is deemed critical to the discussion, however, an authorization may be granted by the Institute.

Confidentiality During the closed session, any information that is discussed and the outcome of any recommendation are considered privileged information. They may not be discussed outside of the closed session. If applicants request support for their applications from Council members, the Council members must respond that they are not permitted to discuss the application. Any inquiry should be referred to Dr. Robert Finkelstein as the Council Executive Secretary, who will then refer the questions to the appropriate staff member for response.

Consideration of Minutes of Previous Council Meeting

The minutes of the Council meeting of May 26-27, 2005, were considered and accepted as written.

Consideration of Dates for Future Council Meetings

The following dates for future Council meetings were reconfirmed:

February 9-10, 2006	(Thursday and Friday)
May 25-26, 2006	(Thursday and Friday)
September 14-15, 2006	(Thursday and Friday)
February 15-16, 2007	(Thursday and Friday)
May 24-25, 2007	(Thursday and Friday)
September 20-21, 2007	(Thursday and Friday)

Other Items

Expedited Review Process Expedited awards are grants within the payline that a designated subset of Council members approve for funding before each Council meeting. The goal is to issue grant awards as quickly as possible. This allows our Grants Management Branch to issue these awards ahead of schedule. While this meeting is held in September which is FY 05, the awards are issued from FY 06 funds. While we were unable to actually expedite any this round, the Grants Management Branch has many of them ready to make awards as soon as the new fiscal year gets underway.

Reports Book The Reports Book consists of applications that have been designated for funding since the last Council meeting. It includes the status of applications that were identified for High Program Priority (HPP) at the May 2005 Council. It is possible that, as funds become available later in the fiscal year, more of the HPP applications may be paid. If so, Council will be informed at the January 2006 Council meeting

Loan Repayment Program The Loan Repayment Program began about four years ago for the purpose of encouraging MDs, MD/PhDs and clinically oriented PhD to go into research careers. This round we had 181applications. Allocating $2.6 M to this program, 51 grants were awarded. Thirty-three were for clinical and 21 for pediatrics research. We are not sure how many have been accepted yet but most of them do.

Introduction of New DER Staff Dr Finkelstein introduced new staff: Dr. Shai Silberberg, a Program Director detailed to the Channels, Synapses and Circuits Cluster from the NINDS intramural program, Dr. Wendy Galpern, a Program Director in the Clinical Trials Cluster, Dr. Mark Scheideler, a Program Director in the Technology Development Cluster, Dr. John Lynch, a Program Director in the Office of Minority Health Research, and Dr. Michelle Jones-London who is serving in two positions as a Program Analyst in the Office of Minority Health Research and with the Office of Communication and Public Liaisons. Lastly, Roxanne Kerr has joined NINDS as the new Executive Officer in the Office of the Director.

III. Report of the Director, NINDS

Dr. Landis provided a report on activities both at the level across NIH and within NINDS:

Cross NIH Activities The Office of Portfolio Analysis and Strategic Initiatives (OPASI). This new office established in the Office of the Director will employ approximately 76 people in three subdivisions. 1) Resource Development and Analysis--Responsible for creating tools to allow us to do portfolio analysis across ICs in a way that we can't do easily now. This office was created in response to concerns that NIH needs to establish cross institute strategic research plans. OPASI is charged with the task of identifying research opportunities or public health needs that we have not addressed in a systematic way– analysis of burden of disease for example would lie in this division. 2) Division of Strategic Coordination--Roadmap. 3) Division of Evaluation and Systemic Assessment--This office will make an effort to look at how our programs are working - could we be doing better.

The first subdivision will ask what are we doing and what should we be doing, the second will be responsible for actually doing things, and the third will do evaluations. It is an effort to develop a coordinated body to develop and evaluate trans-NIH research initiatives. A Director will be recruited and will report directly to Dr. Zerhouni. The Director will be a person with significant scientific skills and recognition. Dr. Landis discussed the establishment of the Division of Strategic Coordination in more detail. This office is an extension of the Roadmap process using shared funds for shared benefit. It will start in FY 06 with 1.1 percent of the NIH budget increasing to 1.7 percent in 2008 and then will grow to 5 percent as the NIH budget grows, consistent with scientific opportunities and public health needs. The plan is that it will stay at 1.7 percent until the NIH budget grows at more than just the inflationary rates. Also like the Roadmap, the funds for grants and contracts will go to each of the Institutes/Centers. One can think of this division as a way of institutionalizing and finding a home for the Roadmap. Projects are not funded forever by the Roadmap – it represents a venture capital fund where projects are initiated with these monies – at the end of ten years, these move out of this source to others.

Council discussion regarding the OPASI office included concerns that this is a tremendous undertaking that might create problems, whereas looking to each Institute to develop a more strategic analysis would be a better way to do this. Other concerns revolved around the transfer of monies from each Institute with the decreasing budget. Dr. Landis indicated that the Office will go forward and suggested that we should be thinking about the products.

K22/R22 Proposal In her review of the K22/R22 proposals, Dr. Landis informed Council that 150 to 200 grants will be awarded across NIH in FY 2007. These are five year awards, two of which the applicant spends being mentored, while with the remaining three the PI must be a faculty member and the award converts to the R mechanism. Foreign fellows are eligible, but they must be working at U.S. institutions.

NIEHS ONES Award Dr. Landis provided information on the NIEHS ONES award which provides five years of support using the R01 mechanism. Nominations are received from institutions for this Outstanding Environmental Scientist award. Little preliminary data is required for the application, 50 percent effort must be dedicated to the project in toxicological research.

Specific NINDS Issues.

Outreach to Advocates Dr. Landis began the NINDS information session by reviewing the outreach efforts over the past few years citing that effective communication is critical to achieving our mission. In 2004 individual meetings with over 60 different patient, voluntary, advocacy and research groups were held. In 2005 NINDS held a nonprofit symposium inviting 200 plus groups with 74 representatives attending. NINDS staff talked to the groups about what the Institute does, how it does it, received feedback on what participants think we do and discussed issues important to them, for example intellectual property issues. In the course of the meeting, the groups came up with a list of topics which will guide the selection of speakers for next year's meeting. Dr. Landis was committed to making this a regular mechanism for interacting with non-government organizations.

NINDS Planning Efforts The outreach to advocates report was a perfect lead into the history of NINDS planning efforts and our plans for the future.

In 1999 NINDS, Dr. Gerry Fischbach's strategic plan involved over 200 people and resulted in the "Neuroscience for the Millennium" plan for the future. One limitation of that effort was that it was theme-based and many felt the plan did not marry the basic science themes related to the diseases in a satisfying way. To begin to address this problem, the Institute has had Parkinson's Disease research planning meetings in 2000, 2003, 2005, a Brain Tumor review group in 2000, a White House Conference on Epilepsy in 2000, and other planning meetings.

Dr. Landis reported that the Institute has been engaged in extensive planning, but that there is a need to coordinate planning across disciplines/diseases.

2006 NINDS Strategic Plan In 2006 we will begin to utilize the portfolio analyses that have been undertaken. We need to integrate theme-based planning with disease-specific plans; need to make sure that the institute is not missing opportunities; need to align our activities with those of other institutes; and need to think about what needs to be done but what can be done by other ICs. We have just decided to initiate this planning process and will be thinking about how we need to conduct it and looking to Council for advice/guidance.

Council was enthusiastic about a new planning effort and put forward examples of other types of planning processes NINDS could use to help model our own. Mr. Martin, who has been a veteran of some of our planning efforts suggested a better definition of the scope of the planning in advance. His thoughts were that some diseases have important projects that require greater mandatory centralization; some specific disease areas may need better organization as well as funding and more multidisciplinary efforts.

IV. Fiscal Year 2006 Budget Discussion

Dr. Finkelstein presented background information on NINDS as the largest NIH funder of Neuroscience Research in his report. He provided a timeline to Council for the time it takes from creating the budget forecast to the final NIH budget passed by Congress. For FY 2006 we are still currently waiting for this number so the presentation represents projections. His report outlined the RPG budget and our commitments to non-competing grants, new competing grant projections and how this all affects the payline. Dr. Finkelstein outlined the Institute's Clinical Trials and large Center Grant programs that play a role in budget adjustments and some of the out year commitments and asked Council to think about how these affect the payline for future years.

His description ended by reporting to Council that after subtracting all the set aside dollars and out year commitments, the projected payline would have been the 10th percentile for FY 2006. Staff have however been able to come up with strategies to increase the payline to the 12th percentile and if the final budget is higher than expected, the Institute would be able to increase the payline further.

Council seemed concerned, while recognizing the limitations of increasing grants and larger project budgets and suggested other methods of increasing the payline, such as bigger cuts for larger program projects or asking non-competing grantees to take cuts in out years.

Dr. Landis said that the IC Directors meet during the year as a group for half a day or day to discuss these issues, and she would be glad to take Council's recommendations to this Board. Interestingly, two years ago a decision was made that NIH would not cut out year commitments. Extensive discussion of outlying years was conducted by Council recognizing that cutting or adjusting outlying years could contribute to a higher payline. Other considerations included that we revisit carryover of funds from year to year. Comments on both pro- and con- were discussed in terms of need for carryover and rationale for allowing the carryover percentage to be as high as 25 percent.

Another discussion involved intramural contributions and how the Institute could tap into these resources.

V. Report of the Director, National Human Genome Research Institute: "HapMap and Complex Disease"

Dr. Francis Collins, Director, National Human Genome Research Institute, reported on the status of different programs currently underway that build upon the foundation laid by the Human Genome Project, which was started in 1990 and successfully completed in April 2003.

One major focus is aimed at developing better and more efficient sequencing technologies, with the short-term goal of lowering the cost of sequencing an individual human genome to $100,000 and the ultimate goal of redu cing the cost to $1,000 or less. Another important effort remains enhancing the research community's ability to compare the genomes of different organisms. At the present time, comparative genomics represents our most powerful means of determining which functional elements have been conserved in the human genome throughout evolution and, consequently, may play a significant role in human health and disease. The current goal is to continue to add the genomic sequences of strategically selected organisms to publicly available databases.

Most of Dr. Collins' talk centered on the International HapMap Consortium, a project in which scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States have partnered to develop a comprehensive map of human genetic variation, or haplotypes. This resource, called the HapMap, will accelerate efforts to find genes associated with common, complex diseases and also with individual response to drugs. Dr. Collins reported that in February 2005, Phase I of the HapMap was completed with more than 1 million single nucleotide polymorphisms (SNPs) genotyped. Over the summer in Phase II, Perlegen added more than 2 million additional SNPs to the map and the final HapMap analysis will be published in the fall of 2005.

While the HapMap provides researchers with an opportunity to do more systematic analyses of the genetic factors involved in human disease, Dr. Collins cautioned that researchers should not jump to conclusions too quickly when using HapMap data to facilitate their genome-wide searches for genes. He emphasized that very large, well-phenotyped clinical cohorts will be needed and that whole-genome association studies may fail if there are multiple, individually rare alleles underlying the disease rather than a major common variant. Because simple stratification can lead to false positives, he urged researchers to apply rigorous standards of statistical significance and to confirm any gene "discovery" by replicating the findings in independent studies that use the same set of SNP markers. He also noted that while whole-genome association studies can narrow the location of a susceptibility variant to a small interval of the genome, follow-up studies will be needed to pinpoint the variant and analyze its function.

In summary, a host of new genomic resources are coming on line that will greatly speed and strengthen investigations into the understanding of genomic function and the genetic factors contributing to common, complex diseases. The availability of the Phase I HapMap has already led to the identification of major gene variants that contribute to common diseases and is expected to open up a new chapter in biomedical research over the next two to three years.

VI. Council Subcommittee Reports

Training, Career Development and Special Programs Subcommittee

Dr. Bruce Bean, Chair of the Training and Career Development and Special Program Subcommittee reported the following:

NIH Wide New Investigator Committee The focus of the committee is to determine how to assist first time R01 applicants to get funded. The success rate of R01 funding is clearly an NIH-wide issue. At Dr. Mobley's request, data were gathered assessing the success rate of new NINDS R01 investigators. Preliminary information provided by Margaret Jacobs suggests that new investigator applications have a first-submission success rate of 7 percent. First amended applications rise to a success rate of 24 percent, but this is based on a very small data set and additional information will be obtained. Dr. Finkelstein recommended that various options for helping new investigators be presented and discussed at the next Council meeting. NINDS will begin to gather information to inform this process.

K Awards Another issue addressed at the Training Subcommittee meeting was a follow up on efforts to improve turn-around time for K awards. Dr. Raul Saavedra has successfully moved up the review time so that, for example, applications received in October/November are reviewed in study section in January. Dr. Landis let Council know that based on their recommendation NINDS is now expediting funding and hence narrowing the gap between the score and Notice of Grant Award.

F32 for Clinicians Also discussed was the proposal by Dr. Mobley to set up a distinct F32 for people in neurology or neurosurgery residency programs. One of the main goals is to assist these potential candidates by having their applications reviewed within the Institute rather than in CSR. There is an issue of whether this would be possible, but the consensus of the subcommittee was that it makes sense and that the idea needed to be brought to Council as a whole. Council had actually discussed this issue four years ago and approved the concept. Dr. Landis mentioned that this was a piece of a large program aimed at enhancing training of physician scientists that had been formerly approved by Council; the question now is do they want to endorse it again and encourage implementation. The Committee recommended that a Neurology/Neurosurgery Clinical Sciences Training Award (NNCSTA) be established that would be reviewed within NINDS.

Neurobiology of Disease Course Finally, a follow up report was given on the Blueprint initiative to develop courses in the neurobiology of disease as part of academic training programs. The RFA received 17 applications; nine have been awarded. Another round is being considered. Dr. Landis underscored that these are for PhD students although could be taken by MDs or MD/PhDs. A prerequisite of the application was that people participate from multiple departments; the ideal course would include multiple basic science and multiple clinical departments. Many of the courses that were highly scored had patient presentations; the objective would be to combine discussions of the phenotype, the disease what is known about the basic biology of the system, the genetics and to generally engage PhD students in the interesting scientific challenges of disease-related research.

Clinical Trials Subcommittee

Dr. Donald Easton, Chair of the Clinical Trials Subcommittee reported the following:

Half of the session involved updates from the Clinical Trials group and other half in closed session so Dr. Easton only reported on the updates from the Clinical Trials cluster.

Conflict of Interest Update The issue was raised about clinical research investigators and the institutions they represent who have a potential conflict of interest by virtue of a financial stake in clinical trials that they are a participant. The Institute is drafting a policy to address the problem with trials funded by NINDS and looking into whether such a policy needs to be NIH wide.

Auditing and Monitoring Clinical Trials The Institute is in the process of renewing an external contract that it has for monitoring and auditing of NINDS-funded clinical trials. Additional information will be presented at a future Council meeting.

Workshop The NINDS is planning a workshop to develop a training program for clinical research fellows to enhance the participation of new investigators in clinical trials.

Emergency Network Initiative An emergency network initiative will begin in 2006 which will create an important link between neurology and emergency medicine for the opportunity to conduct clinical trials of interventions for acute neurological diseases.

Clinical Research Collaboration The clinical research collaboration is underway contacting physicians and potential participants in the NINDS contract effort to connect patients and office based neurologist with NINDS funded research trials.

Common Data Elements NINDS has developed an initial set of common data elements for clinical studies in neurology. They are currently being circulated to investigators for comments in an attempt to bring some uniformity rather than having every trial establish its own data elements.

At the next subcommittee meeting, there will be a report on the outcome of clinical trials and their impact on the American public based on studies that have been completed over past decade. People have been interested in the outcome of NINDS clinical trials. The Committee would also like to look at current clinical trials that had termination dates that were not met in order to assess the factors that contribute to timely completion. Council will examine whether there are similar problems across various kinds of trials or whether they are unique to certain disciplines with the idea that Council will try to help give some thoughtful input.

Dr. Easton ended with the comment that it is clear to the Subcommittee that the Clinical Trials group has become more organized with a lot of new input, ideas and means of seeking out ideas for expansion, and improvement of the quality of clinical trials across the entire Institute.

Basic and Preclinical Programs Subcommittee

Dr. Raymond Dingledine, Chair of the Basic and Preclinical Programs Subcommittee reported on the following three topics:

Report on Neuroscience Blueprint FY 05 and FY 06 Activities and Request for Guidance on Possible FY 07 Initiatives Dr. Dingledine reported on the 2006 initiatives that have been released as either RFAs or contracts. NINDS is the lead IC for a program of expanded, cross-disciplinary neuroscience core grants, with direct costs up to $1,500,000 per year that may serve regional or national needs. Other FY 06 initiatives include developing new ways to image neural activity, establishing neurobiology of disease courses, producing recombinase-expressing transgenic mice, and establishing training programs in translational research, neuroimaging, and neurocomputation/informatics.

In considering the FY 07 initiatives it is useful for NINDS to consider how best to leverage the investment in the Blueprint activity. All of the Neuroscience Institutes contribute Blueprint funds and those proposals that have highest merit will be implemented. Dr. Baughman distributed a list of potential ideas for FY 07. A few that were discussed include:

1. An expanded effort to visualize neuronal activity in vivo in cell circuits and systems, perhaps with multi-institutional participation. For both basic and clinical studies this is a key area for future development.
2. The Neuroscience Information Framework, which was begun as a partnership between the Society for Neuroscience, NINDS, NIMH, and NIDA and with pilot funds from Blueprint in FY 05. This set of databases still needs additional development.
3. Medicinal chemistry support for neuroscience compound development. Increasingly therapeutics and bioactive probe development in neuroscience are limited by the availability of medicinal chemistry resources to optimize compounds. NINDS should not attempt to use research projects to create such resources de novo, but should take advantage of the well developed capabilities available in the private sector by means of contracts or cooperative agreements. Such an effort would complement the NINDS Translational Research Cooperative program, and would cover the gap between the NIH Roadmap Molecular Libraries screening effort and the Roadmap NIH RAID program for late-stage preclinical IND preparation.
4. A proteomics initiative that would build on the foundation of gene expression data that is being considered. Understanding of disease mechanisms and development of better biomarkers for therapeutics development would be greatly accelerated with cutting edge application of proteomic analysis techniques.

Additional suggestions can be submitted during the next two weeks.

Update on FY 06 Implementation Plan for Medical Countermeasures to Chemical Threats Initiative Dr. David Jett led the discussion and reminded members that the President's FY 06 budget allocated $50 million dollars to Medical Countermeasures, with about $35 million allocated to nerve agent-related research. Many of the symptoms of chemical attack are neurologic in nature, including seizures, some neurodegeneration, disorientation, etc. The types of chemical agents being considered are nerve agents, pulmonary agents, metabolic poisons, vesicants etc. The goal of this program is to develop candidate drugs for the nation's defense against chemical attacks. A broad program of cooperative agreements and contracts has been developed in cooperation with NIAID, the lead institute for counterterrorism research at NIH, and with NEI, NIAMS, NIEHS, and NHLBI. Part of this effort will use the NINDS Anticonvulsant Screening Program contract to test promising antiseizure candidates, and a suggestion was made to expand the Utah screening program to screen for neuroprotective therapeutics, which also are important for treating exposure to nerve agents. Secondly, this might be an opportunity to enhance and develop new neurotoxicology training programs. It will be important to engage the neuroscience community broadly in working toward identifying new medical countermeasures for chemical threats.

Assay Development RFA for the Molecular Libraries Roadmap Initiative Dr. Dingledine mentioned that he is one of nine principal investigators for the Molecular Libraries Screening Centers Network (MLSCN). The goal of the program is to develop small molecule probes that perturb the function of protein targets, targets that pharmaceutical companies are not going after, and targets that are of particular biological or physiological relevance. An important issue is how to get the neuroscience community aware of this opportunity and how to get them more involved. With the Assay Development RFA managed by NINDS, an investigator can propose targets and assays in a project plan that is reviewed by study section. The investigators subsequently have the option of applying for screening in the ten screening centers in the MLSCN. An assay project has to have the following characteristics to be useful: 1. Reducible to 96 or 384 well format for both cell based and homogenous liquid based assays; 2. A related validation assay or secondary assay that doesn't have the same readout as the first to validate the hits; 3. An independent tertiary assay that does not need to have high throughput, but which relies on some other feature of the biology that provides selectivity for the hits.

In the present round there are 109 assay proposals that have been peer reviewed and these will be considered in the closed session of Council. These include a range of assays for enzymes, receptors, ion channels, scaffolding proteins and some phenotypic assays. The topics are trans-NIH, but a representative share is neuroscience-related.

VII. Concept Approval for Fiscal Year 2007 Proposed Initiatives

Dr. Finkelstein began his report on the concept approval process by commenting that NINDS is poised to involve Council more in deciding which initiatives to carry forward. A general presentation was done on the initiative process, why initiatives are done and where the ideas for the initiatives come from. Council was provided a list of presentations that will be considered by the various NINDS approval committees and asked for general comments.

A comment from Council seemed to indicate that they might appreciate some kind of ranking from NINDS to give them a better idea of what they consider their priorities. Also a clear, unified format for proposal delivery was requested so that consistent information was provided for each. All initiatives were presented and general comments were discussed by Council and NINDS staff for concurrence and concept approval. Dr. Finkelstein ended by requesting suggestions and comments be sent to him directly.

VIII. Council/Staff Working Group Update

Dr. Finkelstein reported that the Council/Staff Working Group was scheduled to meet following Council adjournment the next day. The project taken on by a subset of members and NINDS staff is to figure out how we can evaluate the success of various kinds of NINDS initiatives. All welcome to come if not part of working group.

IX. NINDS Office of International Activities

Dr. Yuan Liu, Chief, of the Office of International Activities, provided Council with a brief overview of current international activities beginning with the mission of the Office of International Activities and outlining why international neuroscience is important to the NINDS mission.

The health of the American people is part of a bigger challenge of global health and international studies can only benefit the health of the people in the U.S. According to a National Science Foundation report, a quarter of the U.S. scientific publications have international co-authors. The neuroscience community is even more of an international enterprise with nearly one third of the Society for Neuroscience members being from outside the US. This information points to the fact that scientific research is a global endeavor.

Neuroscience research is conducted outside the U.S. in both high and low- to middle-income countries and many research opportunities and resources could be utilized by the U.S. Examples include specific disease populations who are genetically unique or drug naïve, or environmentally influenced diseases or disorders that are not readily found in this country. In particular, unique intellectual talents can be found outside the U.S.

Currently, only a small portion of NINDS' funding is dedicated to the international sector - about 1 percent of awarded grants. By dollar amount this is less than 0.7 percent since the average dollar amount of an international grant is smaller. Approximately 30 percent of our international studies are focused on basic neuroscience, while 70 percent are disease related. Dr. Liu presented an example of disease related international research performed by Dr. Stephen Wilton from Australia. Dr. Wilton developed a very innovative anti-sense oligonucleotide therapy for the treatment of Duchene muscular dystrophy. This was the first research of its kind funded by the NINDS. A major pharmaceutical company has plans to conduct a clinical trial of this very severe but rare disorder based on the results of Dr. Wilton's translational research. Another example was the research to develop a novel brain stimulation to enhance stroke recovery by Dr. Esteban Fridman from Argentina. After receiving training in an NINDS intramural laboratory, Dr. Fridman returned to his home country with support from the GRIP initiative (see below). Dr. Fridman's non-invasive research combines magnetic stimulation and behavioral training to treat stroke patients. His approach, if successful, could benefit stoke rehabilitation in the U.S.

The NINDS currently leads and participates in several trans-NIH international initiatives:

1. Brain Disorders in the Developing World: Research across the Lifespan. A creative program to encourage collaborations between high and low- to middle-income countries to study brain disorders.
2. International Clinical, Operational, and Health Services Research Training Award (ICHORTA) AIDS/TB. Encourage collaborations between US and low- to middle-income countries to study AIDs related health problems.
3. International Neuroscience Fellowship (INF). Support research training of junior or mid-career foreign neuroscientists and/or clinicians in a US laboratory for one to two years.
4. Global Health Research Initiative Program (GRIP). Assist NIH-trained foreign young investigators return home to establish independent research.
5. Fogarty International Research Collaboration Award (FIRCA). Fosters international research partnerships between NIH-supported U.S. scientists and their collaborators in low- to middle-income countries.
6. US-Japan Brain Research Cooperation Program. This program supports scientist exchange and joint workshops between U.S. and Japanese neuroscientists.
7. International Neuroinformatics and Computational Neuroscience. The collaborative nature of these areas definitely requires international cooperation. The OIA is making a big effort to leverage international support to further research opportunities in these areas.

Items to consider include how best to identify international neuroscience research opportunities, how to take advantage of global human and technological resources in neuroscience and how to best incorporate international neuroscience to help NINDS achieve its mission. Dr. Liu reported to Council that future directions would include recruiting other institutes to join the International Neuroscience Fellowship Program, perhaps through the Neuroscience Blueprint Institutes; and the recruitment of other countries to develop initiatives similar to the US-Japan Brain Research Cooperation Program.

X. Council Review of Pending Applications

This portion of the meeting, involving specific grant review, was closed to the public. The Council gave special attention to applications from foreign institutions and other applications, which needed specific discussion.

Research Training and Career Development Programs

The Council reviewed a total of 112 research career development and institutional training grant applications; of this total, 72 applications had primary assignment to NINDS, and 50 of them (64.4 percent) were recommended for support in the amount of $7.0 million first-year direct costs. It is anticipated that, of the research career development and institutional training grant applications competing at this Council, NINDS will be able to pay first-year direct costs of approximately $1.8 million.

Research Grant Awards

The Council reviewed a total of 2,428 research grant applications; of this total, 1,382 applications had primary assignment to NINDS, and 842 of them (60.9 percent) were recommended for support in the amount of $228.6 million first-year direct costs. It is anticipated that, of the research grants competing at this Council, NINDS will be able to pay first-year direct costs of approximately $46.3 million.

Senator Jacob Javits Neuroscience Investigator Awards

The Senator Jacob Javits Neuroscience Investigator Awards are made to distinguished investigators who have a record of scientific excellence and productivity, who are actively pursuing an area of research of strategic importance, and who can be expected to continue to be highly productive for a seven-year period. Candidates are nominated and selected at each Council meeting. At this meeting, the Council recommended one investigator as a Javits awardee.

Small Business Innovation Research and Small Technology Transfer Award Programs

The Council reviewed a total of 194 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 106 applications had primary assignment to NINDS and 70 of them (66.0 percent) were recommended for support in the amount of $13.3 million first-year direct costs. It is anticipated that, of the SBIR and STTR applications competing at this Council, NINDS will be able to pay first-year direct costs of approximately $3.0 million.

XI. Adjournment

The meeting was adjourned at 10:20 a.m. on Friday, September 16, 2005.

We certify that, to the best of our knowledge, the foregoing minutes and attachments are accurate and complete.

Robert Finkelstein, Ph.D.
Executive Secretary
National Advisory Neurological Disorders
and Stroke Council

Director, Division of Extramural Research
National Institute of Neurological Disorders and Stroke

Story C. Landis, Ph.D.
Chairperson
National Advisory Neurological Disorders
and Stroke Council

Director National Institute of Neurological Disorders and Stroke

These minutes will be formally considered by the Council at its next meeting. Corrections or notations will be incorporated in the minutes of that meeting.

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¹ For the record, it is noted that members absent themselves from the meeting when the Council is discussing applications (a) from their respective institutions or (b) in which a real or apparent conflict of interest might occur.

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