Received: from JNET-Daemon by UNCVX1.BITNET; Wed, 16 Jan 91 14:58 EDT
Received: From UNC(MAILER) by UNCVAX1 with Jnet id 0117 for PJONES@UNCVAX1;
 Wed, 16 Jan 91 14:58 EST
Date: Wed, 16 Jan 91 14:56 EST
From: Dot Baker <UNCDOT@UNC.BITNET>
Subject: RFANS/AG-91-03   January l8, l99l NIH Guide
To: pjones@UNCVX1.BITNET

Hi,
 This is the fifth of six.  Please post to the NIH Listserver as:
    RFANS/AG-91-03.910118
Thanks     Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR APPLICATIONS
 
ALZHEIMER'S DISEASE AND RELATED CEREBRAL DEGENERATIVE
DISORDERS
 
RFA:  NS/AG-91-03
 
P.T. 34; K.W. 0715180, 0705010, 0710010, 1002030, 0755030, 0765033
 
National Institute of Neurological Disorders and Stroke
National Institute on Aging
 
Letter of Intent Receipt Date:  April 1, 1991
Application Receipt Date:  May 6, 1991
 
PURPOSE
 
The National Institute of Neurological Disorders and Stroke
(NINDS) and the National Institute of Aging (NIA) are
inviting research grant applications on the etiology,
pathogenesis, and diagnosis of Alzheimer's disease and
related cerebral degenerative disorders.
 
The importance of expanding support for Alzheimer's disease
research has been widely recognized by the Federal
Government.  The U.S. Senate Appropriations Committee
report for Fiscal Year 1991 placed particular emphasis on
Alzheimer's disease and provided considerable additional
funds for expansion of the activities of the NIA and NINDS
in this area.  The Advisory Panel on Alzheimer's Disease of
the Department of Health and Human Services (DHHS) issued a
special report on Alzheimer's disease (DHHS Pub. NO [ADM
89-1664]) urging that the Federal research budget for
Alzheimer's disease be substantially increased.  The
implementation plan for the Decade of the Brain developed
by the National Advisory Neurological Disorders and Stroke
Council also emphasized the need for enhanced funding of
research on dementias.  It is widely appreciated that there
are many scientific opportunities that can be taken
advantage of and significant progress can be made in
understanding the neurodegenerative diseases of later life,
especially Alzheimer's disease.  Many governmental and
private groups and individuals are urging that the research
momentum be increased by expansion of research efforts on
etiology, pathogenesis, diagnosis, and treatment of
Alzheimer's disease and related disorders.
 
BACKGROUND
 
Present estimates indicate that as many as 4 million
Americans suffer from Alzheimer's disease (AD) or related
cerebral degenerative disorders.  The personal and societal
burden of these disorders is enormous as a result of the
relentless and devastating course of the deterioration.
The total cost of caring for individuals with AD and
related disorders has been estimated at $90 billion
per year.  The personal and societal costs of these
disorders underline the urgent need for an increase in
research efforts.
 
RESEARCH GOALS AND SCOPE
 
The NINDS/NIA are soliciting innovative research projects
designed to elucidate the etiology and pathogenesis of
Alzheimer's disease and related degenerative  disorders as
well as studies aimed at improving diagnosis and treatment.
Individuals new to these areas of research as well as
established investigators are encouraged to submit research
proposals (R01) to enhance ongoing research and to
investigate new ideas that are exploratory in nature.  When
practical, applicants are encouraged to consider submitting
applications that utilize and collaborate with existing
resources of the NIA-funded Alzheimer's Disease Research
Centers (ADRCs) or the Alzheimer's Disease Center Core
Grants (ADCCs), thus contributing to cost savings by
utilization of already funded research resources such as
the clinical and autopsy cores of these centers.
 
The need for new knowledge concerning the dementias of old
age covers a broad spectrum of topics.  The following topics
are suggested to highlight some examples of areas that
could benefit by increased attention.  The research topics
indicated below are not intended to be an exhaustive or
exclusive listing of interests.  The list is compiled
merely to indicate examples of topics.  Applications on
other related topics and problem areas are welcome.
 
o   Genetics:  Both environmental and genetic factors have
been suggested or implicated in the etiology of AD and
other cerebral degenerative disorders.  Autosomal dominant
inheritance of AD has been demonstrated in certain
pedigrees and tentative map locations for familial AD
(FAD) genes have been identified.  The heterogeneity of AD
etiologies is indicated by the different genetic loci
implicated and also by differences in age of onset in FAD
families.  While most cases of AD occur sporadically, many
investigators believe that were a gene discovered for
familial forms of AD (FAD), it would likely shed
light on other potential causes.  Much research is needed
on the mechanisms of interaction between aging processes
and the expression of a gene for a disorder of late life
onset.  Further studies are needed as well to clarify the
relationship between genetic and possible environmental
factors (e.g., aluminum, certain viruses).  The similarity
of symptoms and pathology of Alzheimer's
disease and adult Down's syndrome remains to be explained.
 
o   Mechanisms of Cell Death:  A major unanswered question
in AD is the cause of neuronal dysfunction and eventual
death of neurons.  Neurons in certain regions of the brain
appear to exhibit selective age-related vulnerability to
cell death.  Studies are encouraged on the selective
vulnerability of neuronal systems and the processes of
neuronal degeneration in AD and related degenerative
diseases of late life.
 
o   Nerve Growth Factors:  The infusion of nerve growth
factor has reversed the loss of memory in old rats and rats
with certain cholinergic lesions.  Other factors have been
identified recently that may be neurotrophic for other
types of neurons.  Additional work in this area is
necessary to evaluate the effect of these trophic
substances on model systems for the multiple
neurotransmitter deficits present in AD.  Studies related
to the potential therapeutic role of nerve growth factors
in AD are strongly encouraged.  The NIA sponsored Working
Group on Nerve Growth Factors recommended a number of lines
of inquiry requiring pursuit for further development of the
therapeutic potential of such agents (Phelps et al., 1989,
Neurobiology of Aging, 10, 205-207).
 
o   Animal and Other Model Systems:  The development of new
animal models is critical to progress in the study of AD
and related neurodegenerative diseases.  Research oriented
toward useful animal and cell culture model systems is
encouraged.  Data from aging primates and dogs may reflect
processes closely related to AD.
 
o   Neuroimaging:  Further investigations are needed to
understand and resolve conflicting data derived from the
multiple approaches to imaging the aging brain, both normal
and pathological.  Greater precision is essential in the
localization of physiologic and anatomic dysfunctions that
produce the clinical symptomatology seen in dementing
disorders.  Research on methods for merging data from PET
and MRI in AD and related cerebral neurodegenerative
diseases would be useful in resolving these questions.
 
o   Differential Diagnosis:  Early and accurate diagnosis
of AD has a major impact on the progress of research on
dementia.  Research is needed to refine existing diagnostic
procedures and/or to develop more sensitive and reliable
techniques.  The relationship between AD and other
dementias, such as vascular dementia, Parkinsonian
dementia, Pick's disease, Creutzfeld-Jakob disease, and
diffuse Lewy body disease needs to be addressed.  Sensitive
and specific biological and chemical markers to identify
those at high risk of AD and those in the very early stages
of AD are required.  Some of the recommendations of a 1987
Consensus Development Conference on the Differential
Diagnosis of Dementing Diseases for future research in this
area included:  exploration of potential biological
diagnostic markers with special emphasis on families with
autopsy-diagnosed dementias; evaluation of neuroimaging by
long-term follow-up of patients, correlation with clinical
and neuropsychological findings, and tissue histopathology;
evaluation of current neuropsychologic instruments in
populations that differ in age, education, ethnic
composition, and social or cultural background, using
long-term follow-up and correlation with clinical,
neuroimaging, and neuropathologic findings; and design of
multivariate studies to determine the optimal combination
of diagnostic strategies needed to differentiate the
dementias common in each age group.
 
MECHANISM OF SUPPORT
 
The mechanism of support for this RFA will be the individual
research grant (R01).  Applicants may request up to 5 years
of funding support.  Funds will not be provided to cover
the costs of patient health care.  Funds may be requested
to cover costs related to participation of research
patients in clinical protocols.
 
It is expected that at least 20 awards will be made.  The
specific number will depend on the merit and total costs of the
applications.  These applications are not
expected to compete for funding within the general pool of
dollars available for investigator-initiated research
grants.
 
While no future funds are set-aside, awards made in
response to this RFA may be renewed through the submission
of a competitive renewal application.
 
METHOD OF APPLICATION
 
LETTER OF INTENT:
 
The NINDS and the NIA urge applicants to submit a letter of
intent to both Dr. Oliver and Dr. Banner, at the addresses
listed below, no later than April 1, 1991.  While a letter of
intent is not required, is not binding, and does not enter
into the review of the application, it
allows NINDS/NIA staff to plan for the review of
applications and to avoid possible conflict of interest in
the selection of reviewers as well as to ensure that
potential applicants receive relevant program information
prior to expending considerable effort in application
preparation.  The letter of intent should include the name
and affiliation of the principal investigator, the names
and affiliation of co-investigators, a descriptive title of
the project, and identification of all
collaborating institutions.
 
FORMAT OF APPLICATIONS:
 
The application must be submitted on the 10/88 revision of
the form PHS 398.  Application kits may be secured from
institutional offices of grants and contracts or from:
Office of Grants Inquiries/ DRG, NIH/ Westwood Building,
Room 449/ 5333 Westbard Avenue/ Bethesda, Maryland 20892.
 
To identify these applications as being in response to the
RFA, check "yes" on item 2 of page 1 of the application and
enter the title:  "NINDS/NIA ALZHEIMER'S DISEASE"  and the
RFA number NS/AG-91-03.  The RFA label available in the
10/88 revision of the Application Form 398 must be affixed
to the bottom of the face page.  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 the
review.  All policies and requirements that normally
govern the grant programs of the Public Health Service
apply.
 
APPLICATION PROCEDURE:
 
The deadline for receipt of applications by the NIH
Division of Research Grants (DRG) is May 6, 1991.  Send or
deliver the completed application and four (4) signed,
exact photocopies of the application to:
 
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, MD  20892**
 
In addition, send one (1) exact photocopy to Dr. Oliver and
one (1) exact photocopy to Dr. Banner at the addresses
listed below.
 
Applications must be received by May 6, 1991.  An
application not received by this date will be considered
ineligible for consideration under this solicitation.  The
review for scientific and technical merit of applications
judged responsive to the RFA will take place in June/July
1991, and NINDS and NIA Council review will be in September
1991.  Awards will be made by September 30, 1991.
 
REVIEW PROCEDURES AND CRITERIA
 
REVIEW METHODS:
 
Upon receipt, applications will be reviewed by NINDS and
NIA staff to determine administrative and programmatic
responsiveness to this RFA.  Applications judged
unresponsive will be returned to the applicant.  NOTE:
APPLICATIONS THAT DO NOT CONFORM TO THE INSTRUCTIONS
CONTAINED IN THE PHS 398 (REV. 10/88) APPLICATION KITS WILL
BE JUDGED NONRESPONSIVE AND WILL BE RETURNED TO THE
APPLICANT.
 
All applications that are complete and responsive to this
RFA may be subjected to a triage by a peer review group to
determine relative scientific merit among the applications.
Applications judged to be noncompetitive for award will be
administratively withdrawn.  Applicant Principal
Investigator and institutional business official will be
notified.
 
If the application submitted in response to this RFA is
substantially similar to a research grant application
already submitted to the NIH for review, but that has not
yet been reviewed, the applicant will be asked to withdraw
one of the applications.  Simultaneous submission of
identical applications will not be allowed, nor will
essentially identical applications be reviewed by different
review committees.  Therefore, an application cannot be
submitted in response to this RFA that is essentially
identical to one that has already been 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.
 
Those applications judged to be competitive for award will
be further reviewed for scientific and technical merit by
an initial review group convened by the Division of
Extramural Activities, NINDS, during June/July 1991.  A
final level of review will be by the National Advisory
Neurological Disorders and Stroke Council and National
Advisory Council on Aging.
 
REVIEW CRITERIA:
 
The factors to be considered in the evaluation of each
application will be similar to those used in the review of
traditional research grant applications.  The major factors
to be considered in the evaluation of applications will
include:  the scientific merit of the proposed project,
including the originality and feasibility to the approach,
and the adequacy of the experimental design; the competence
of the investigator(s) to accomplish the proposed research
goals, their commitment, and the time they will devote to
the research; the adequacy of facilities for performance of
the proposed research, including the laboratory facilities,
the proposed instrumentation, and, when needed, the data
management systems; the integration of any
interdisciplinary components into a coherent enterprise
with adequate plans for interaction and communication of
new information and concepts among the collaborating
investigators; and the appropriateness of the budget for
the proposed research.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that
research findings can be of benefit to all persons at risk of the
disease, disorder or condition under study; special emphasis
should be placed on the need for inclusion of minorities and
women in studies of diseases, disorders and conditions which
disproportionately affect them.  This policy is intended to apply
to males and females of all ages.  If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear
compelling rationale should be provided.
 
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group.  In
addition, gender and racial/ethnic issues should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study.  This information should be
included in the form PHS 398 in Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility
of including the broadest possible representation of minority
groups.  However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
 
The rationale for studies on single minority population groups
should be provided.
 
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including but not limited to
clinical trials.
 
The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
 
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
 
If the required information is not contained within the
application, the application will be returned.
 
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies.  If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
 
All applications for clinical research submitted to NIH are
required to address these policies.  NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
 
INQUIRIES:
 
For further information, potential applicants should write
or call:
 
Eugene J. Oliver, Ph.D.
Demyelinating, Atrophic, and Dementing Disorders
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Federal Building, Room 806
Bethesda, MD  20892
Telephone:  (301) 496-1431
 
Carl D. B. Banner, Ph.D.
Program Director, Etiology of Alzheimer's Disease
Dementias of Aging Branch, NNA
National Institute on Aging
National Institutes of Health
Building 31, Room 5C35
Bethesda, MD  20892
Telephone:  (301) 496-9350
 
The programs to which the intended grants relate are
described in the Catalog of Federal Domestic Assistance,
entries number 93.853 ("Clinical Research Related
Neurological Disorders"), 93.854 ("Biological Basis
Research in the Neurosciences"), and 93.866 ("Neuroscience
and Neuropsychology of Aging").  Grants will be awarded
under the authority of the Public Health Service Act, Title
IV, Section 301 (Public Law 78-410, as amended; 42 USC 241)
and administered under PHS grant policies and Federal
Regulations 42 CFR Part 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.

