NIH Guide, Volume 26, Number 38, November 21, 1997

RFA:  NS-98-001


National Institute of Neurological Disorders and Stroke

Letter of Intent Receipt Date:  January 15, 1998
Application Receipt Date:  April 24, 1998


In response to recent research progress and opportunity, and in recognition of
Congressional interest to intensify and to expand basic and clinical research in
Parkinson's Disease, the National Institute of Neurological Disorders and Stroke
(NINDS) invites qualified investigators to submit grant applications for the
establishment of NINDS Parkinson's Disease Research Centers of Excellence.  The
purpose of this Request for Applications (RFA) is to encourage additional
research opportunities and discoveries that will lead to improved diagnosis and
treatment of patients with Parkinson's Disease, based on a better understanding
of the fundamental cause(s) of the disease.  It is expected that these Centers
will foster an environment that will enhance the research effectiveness of
investigators in a multi-disciplinary setting, utilizing specialized methods
relevant to the study of Parkinson's Disease.


The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, þParkinson's Disease Research
Centers of Excellenceþ is related to the priority area of chronic disabling
conditions.  Potential applicants may obtain a copy of "Healthy People 2000"
(Full Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government Printing
Office, Washington, DC 20402-9325 (telephone 202/512-1800).


Applications may be submitted by domestic, for-profit and non-profit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of State and local governments, and eligible agencies of the
Federal government. Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.


The mechanism of support for the NINDS Parkinson's Disease Research Centers of
Excellence is the research Center grant (P50).  Responsibility for planning,
direction, and execution of the proposed research centers will rest solely with
the applicant.  Because the nature and scope of the research proposed in response
to this RFA may vary, it is anticipated that the size of the award may also vary. 
It is expected that grants will not exceed $1 million per year direct costs for
five years.  This RFA is a one time solicitation.  Future unsolicited new and
competing continuation applications will compete with all investigator-initiated
applications and be reviewed according to the customary peer review procedures. 
In certain meritorious circumstances, and upon recommendation of the National
Advisory Neurological Disorders and Stroke Council, some applicants who do not
receive P50 grants may be awarded exploratory (Developmental) P20 grants for
$350,000 direct costs or less per year for three years.  (See below)

Investigators seeking to carry out pilot studies of clinical research in
preparation for a clinical trial are encouraged to make use of the þNINDS Pilot
Clinical Trial Grant For Neurologic Diseaseþ as described in Program Announcement
PAR-91-103, August 29, 1997, in lieu of such studies being funded as part of the
center grant.  However, close collaboration and integration between research
center activities and clinical trials is strongly encouraged.


The NINDS will allocate up to $5 million in total costs to support Centers
responding to this RFA in FY 1998.  It is anticipated that up to three Center
grants (P50) may be awarded.  Applicants may request up to five years of support. 
In special instances where applications are received from groups that show high
potential but are judged not fully developed as Centers, a developmental center
grant (P20) may be awarded.  This decision will be based upon the evaluative
comments of the peer review group and the recommendation of the Advisory Council. 
The P20 awards may not exceed $350,000 direct costs per year.  In all cases,
facilities and administrative (indirect) costs will be awarded based on the
negotiated rates.  The award of grants pursuant to this RFA is contingent upon
the receipt of a sufficient number of high quality applications and the
availability of funds for this purpose.  Policies that govern research grant
programs of the National Institutes of Health are applicable to all procedures
in the receipt, review and support of this RFA.


The overall purpose of this RFA is to support and develop outstanding Parkinson's
Disease Research Centers of Excellence that will advance the understanding of
Parkinson's Disease and related movement disorders.  It is anticipated that each
center will contain both basic and clinical research in proportions that are
appropriate for the research objectives.  A broad unifying theme is often helpful
in defining the integration of both clinical and basic research projects. 
Emphasis is placed on multi-disciplinary and collaborative studies that can best
be carried out in a center setting.  The organizational structure of the Center
should be flexible to allow the expeditious application of new basic findings and
new technological developments to clinical research.  Experimental studies may
focus on many significant topics that might include, but are not limited to,
diagnostic, anatomical, pathological, biochemical, genetic, physiologic, or
pharmacologic approaches to elucidating pathophysiological mechanisms of
Parkinson's Disease and related movement disorders.  To generate new ideas and
develop young investigators, each center should have a research training
component containing appropriate types of research training in either the basic
or clinical arena, that is described as a separate project.

New research techniques have created extraordinary opportunities for further
exploration into the etiology and pathogenesis of Parkinson's Disease and related
neurodegenerative disorders.  Topics of investigation within a center might
include, but are not limited to:

Clinical studies of Parkinson's Disease and Parkinsonism.

Development of therapeutic technology related to Parkinson's Disease, including
surgical ablation and brain stimulation, cell implantation and gene therapy.

Identification of multiplex families with Parkinson's Disease; identification and
function of the involved genes and their protein products.

Development of animal models and their use for investigation of pathophysiology
and efficacy of therapeutic intervention.

Development and function of the basal ganglia, motor systems, related brain
areas, their connections and their cellular components.

Molecular and cell biology of the dopaminergic systems and their function in the

Cellular and molecular mechanisms of cell injury and death in Parkinson's Disease
and related neurodegenerative disorders.

Growth factors relevant to Parkinson's Disease.

Structure, function and role of proteins such as alpha-synuclein, which are
implicated in the pathogenesis of the disease.

Imaging technology to examine the progression of disease and the efficacy of
therapeutic interventions.

Composition, formation and role of Lewy bodies and other cellular inclusions in
Parkinson's Disease.


It is the policy of the NIH that women and members of minority groups and their
subpopulations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification is provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 20, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No.
11, March 28, 1994.


Prospective applicants are asked to submit, by January 15, 1998, a letter of
intent that includes a descriptive title of the proposed research, the name,
address, and telephone number of the Principal Investigator, the identities of
other key personnel and participating institutions, and the number and title of
the RFA in response to which the application may be submitted.  Although a letter
of intent is not required, is not binding, and does not enter into the review of
a subsequent application, the information that it contains allows Institute staff
to estimate the potential review workload and avoid conflict of interest in the

The Letter of Intent is to be sent to:

Eugene J. Oliver, Ph.D.
Division of Stroke, Trauma and Neurodegenerative Disorders
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 806
Bethesda, MD 20892


The Research grant application form PHS 398 (rev. 5/95) is to be used in applying
for these grants.  These forms are available at most institutional offices of
sponsored research and from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301/710-0267, email:

The NINDS Guidelines for the development of Program Project and Center
Applications should be followed when preparing the application.  They are
available by accessing the NINDS home page on the Internet
(, Funding Information, Research Grant and
Award Mechanisms, Program Project Grants, and Guidelines.

The RFA title and number must be typed on line 2 of the face page of the
application form and the YES box must be marked.  In addition, the RFA label
available in the PHS 398 (rev. 5/95) application form must be affixed to the
bottom of the face page of the application.  Failure to use this label could
result in delayed processing of the application such that it may not reach the
review committee in time for review. 

Submit a signed, typewritten original of the application, including the
Checklist, and three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

In order to facilitate the review of applications, two additional copies of the
application must be sent to:

Dr. Lillian Pubols
Scientific Review Branch
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 9C10
Bethesda, MD  20892-9175

Applications must be received by April 24, 1998.  If an application is received
after that date, it will be returned to the applicant without review.  The Center
for Scientific Review (CSR) will not accept any application in response to this
RFA that is essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application.  The CSR will not accept any
application that is essentially the same as one already reviewed.  This does not
preclude the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction addressing the
previous critique.


Applications will be reviewed for completeness by the CSR and responsiveness to
the RFA by NINDS. Applications that are complete and responsive to the RFA will
be reviewed for technical merit by  a special review panel convened by the NINDS.

As part of the initial merit review, all applications will receive a written
critique, undergo a process in which only those applications deemed to have the
highest scientific merit (generally the top half of the applications received for
review) will be discussed, assigned a priority score, and receive a second level
review by the NINDS Advisory Council.  Upon recommendation of the initial peer
review group and the NINDS Council, grant applications that lack, for example,
sufficient preliminary data to justify funding as Centers of Excellence, but are
otherwise meritorious, may be recommended for Developmental grants (P20).  The
annual direct costs for P20 grants will not exceed $350,000 for each of three
years.  Applications for Developmental (P20) grants will not be accepted
directly.  Site visits are not anticipated for these Center grant applications.

Review Criteria for Research grant applications: 

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In the
written review, comments on the following aspects of the application will be made
in order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals.  Each of these criteria will
be addressed and considered in the assignment of the overall score.

(1) Significance.  Does this study address an important problem?  If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this

(2) Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

(3) Innovation.  Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative?  Does the project challenge existing
paradigms or develop new methodologies or technologies? 

(4) Investigator. Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

(5) Environment.  Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements?  Is there evidence of institutional support?

Center specific criteria which are described in the NINDS Guidelines for Program
Project and Research Center Grants will also be part of the review.  The criteria
define the distinguishing features of a Center, the organizational and
administrative structure, the budget and timetable for the work, and the
appropriateness of core facilities.  These criteria include:

Unifying theme.  Is there a unifying well defined goal or area of research to
which each project relates and contributes?  Does the goal produce a synergistic
research environment built upon the creative strengths of each component?

Program director.  Does the program director possess recognized scientific,
administrative and leadership abilities and make a time commitment that assures
the maintenance of a high quality program?

Components.  Does the Center grant contain a minimum of three highly meritorious,
integrated research components?  Are the individual investigators responsible for
these projects expert in the areas for which they are responsible, and are they
committed to the entire program?

Organizational and administrative structure.  Are the lines of authority,
responsibility and advisory roles clearly described for the research projects and

Budget.  Is the proposed budget appropriate to the research effort and goals?

In addition, the adequacy of plans to include both genders and minorities and
their subgroups as appropriate for the scientific goals of the research will be

The initial review group will also examine the provisions for the protection of
human subjects, the safety of the research environment, and conformance with the
NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical


Inquiries concerning this RFA are encouraged.  The opportunity to clarify any
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Eugene J. Oliver, Ph.D.
Division of Stroke, Trauma and Neurodegenerative Disorders
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 806
Bethesda, MD  20892
Telephone:  (301) 496-5680
FAX:  (301) 480-1080

Direct inquiries regarding fiscal matters to:

Pat Driscoll
Grants Management Branch
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 1004
Bethesda, MD  20892-9190
Telephone:  (301) 496-9231
FAX:  (301) 402-0219


This program is described in the Catalog of Federal Domestic Assistance No.
93.853.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241
and 285) and administered under PHS grants policies and Federal Regulations 42
CFR 52 and 45 CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.

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