Release Date:  December 18, 1998

RFA NUMBER:  NS-99-004


National Institute of Neurological Disorders and Stroke

Letter of Intent Receipt Date:  January 15, 1999
Application Receipt Date:  April 27, 1999


In response to recent research progress and opportunity, the excellent response
to the initial request, and in recognition of continuing 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
reissuing 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 and related neurodegenerative disorders,
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 these disorders.  The
original RFA was published in the NIH Guide, Volume 26, Number 38, November 21,


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, Parkinson's Disease Research
Centers of Excellence" 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 one million dollars per year direct
costs for five years.  This RFA is a one-time solicitation.  Future 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 may be awarded
exploratory/developmental (P20) grants for $350,000 direct costs or less per year
for three years.

Investigators seeking to carry out pilot studies of clinical research in
preparation for a clinical trial are encouraged to make use of the "NINDS Pilot
Clinical Trial Grant (R01) For Neurologic Disease" as described in Program
Announcement PAR-97-103, 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 dollars in total costs to support Centers
responding to this RFA in FY 1999.  It is anticipated that up to five Center
grants 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 cost per year.  In all cases,
facilities and administrative (F&A) 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 initiative is to continue to support and develop
outstanding Parkinson's Disease and related neurodegenerative disorders research
centers of excellence.  Each center may contain either basic or clinical research
or proportions of each 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 will focus on many significant topics
that might include, but are not limited to, anatomical, pathological,
biochemical, genetic, physiologic, or pharmacologic approaches to elucidating
pathophysiological mechanisms of Parkinson's Disease and related disorders. 
Clinical studies comparing the efficacy and safety of new surgical therapies and
their long term outcome are particularly encouraged.  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, pathogenesis, diagnosis and treatment of
Parkinson's Disease and related neurodegenerative disorders.  Topics of
investigation within a center might include, but are not limited to:

o  Clinical studies of Parkinson's Disease, parkinsonism, and related disorders.

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

o  Identification of multiplex families with Parkinson's Disease; identification
of genes that are directly involved or that increase the risk of disease.

o  Structure, function, composition, role, and possible interrelationship of
proteins and inclusion bodies implicated in the pathogenesis of Parkinson's
Disease and related disorders.

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

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

o  Molecular and cell biology of the dopaminergic systems and other relevant
neurotransmitters and neuromodulators and their function in the brain.

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

o  Exploration of trophic factors and their receptors that promote the survival
of dopamine neurons in the adult brain.

o  Neuronal reconstruction using engineered cell lines that are relevant to
Parkinson's Disease.

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


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 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No.
11, March 18, 1994.


It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there is scientific or ethical reasons not to include them.  This
applies to all initial (Type 1) applications submitted for receipt dates after
October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for Grants
and Contracts, March 6, 1998, and is available at the following URL address:


Prospective applicants are asked to submit, by January 15, 1999, 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 NINDS 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. 4/98) is to be used in applying
for these grants.  These forms are available at most institutional offices of
sponsored research; from the Division of Extramural Outreach and Information
Resources, National Institutes of Health 6701 Rockledge Drive, Room MSC 7910,
Bethesda, MD 20892, 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 on the NINDS home page at:

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. 4/98) 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:

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, mail or deliver two copies of
the application 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 27, 1999.  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.


Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness by NINDS.  Incomplete and/or non-responsive applications will be
returned to the applicant without further consideration.  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 have compelling
potential for development, may be recommended for Developmental grants (P20). 
Site visits are not anticipated for these Center grant applications.

Review Criteria

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


Funding decision will be based on scientific and technical merit as determined
by the Initial Review Group, review by the National Advisory Neurological
Disorders and Stroke Council, and the availability of funds.


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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