POST-POLIO SYNDROME
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NIH GUIDE, Volume 21, Number 5, February 7, 1992
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PA NUMBER:  PA-92-40

P.T. 34; K.W. 0715125, 0785055, 0765035, 0710070, 0755020

National Institute of Neurological Disorders and Stroke

PURPOSE

The National Institute of Neurological Disorders and Stroke (NINDS)
encourages the submission of applications for research grants related to
the post-polio syndrome.  The NINDS invites grant applications to
support research in all aspects of the post-polio syndrome including
epidemiology, diagnosis, pathophysiology, immunology, therapy, and the
development of animal models.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention goals of "Healthy People 2000," a
PHS-led national activity for setting priorities.  This program
announcement, Post-polio Syndrome, is related to the priority area of
diabetes and chronic disabling conditions.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  No. 07-001-00474-0,
or Summary Report:  Stock No. 07-001-0043-1) through the Superintendent
of Documents, Government Printing Office, Washington, DC 20402-9325
(Telephone:  202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State or local governments,
and eligible agencies of the Federal government.  Applications from
minority individuals and women are encouraged.

MECHANISMS OF SUPPORT

Support for this program announcement will be the Research Project Grant
(R01), Research Program Project (P01), Research Center Grant (P50), and
First Independent Research Support and Transition (FIRST) Award (R29).
Prospective applicants are encouraged to communicate with the NINDS
staff contact listed under INQUIRIES regarding the appropriate funding
mechanism.  Both basic science and clinical investigations are
encouraged to address relevant research issues.

RESEARCH OBJECTIVES

Background

Survivors of paralytic poliomyelitis have begun to suffer renewed
neurological and neuromuscular symptoms decades after maximum recovery
from the acute disease.  Symptoms include a form of progressive muscular
atrophy that involves new muscle weakness affecting certain muscle
groups, pain, fatigue, and decreased physical endurance.  Individuals
who have fully recovered from the initial episode and those who still
have residual effects are at risk.  A number of terms have been proposed
to describe these late effects including post-polio syndrome, post-polio
motor neuron disease, and post-polio muscular atrophy.

Estimates of the number of survivors of paralytic poliomyelitis in the
United States vary widely, from about 250,000 to over 1 million.  A 1984
epidemiological study performed by the Mayo clinic found that 25 percent
of survivors had renewed symptoms, but a later follow-up of a sample of
the original respondents showed that 66 percent were experiencing new
weakness.

Pathologic mechanisms involved in the post-polio syndrome are not
understood, and there is evidence supporting several etiological
theories.  Changes in the motor neuron have been studied extensively.
After recovery from acute polio, axons of surviving motor neurons sprout
to reinnervate muscles whose original motor neuron did not survive.  It
is hypothesized that this process is ongoing for several years, after
which the capacity of the motor neuron to reinnervate additional muscles
is reached and the nerve terminals begin to degenerate.

A recent report of IgM antibodies to the polio virus in some patients
with recurring weakness suggests that late effects of the long dormant
polio virus may play a role.  Other hypotheses that have been studied
include neuromuscular changes caused by premature aging in polio
patients, an immunological mechanism, and spinal cord changes affecting
motor neurons.

Research Goals and Scope

Multidisciplinary or collaborative studies of post-polio syndrome are
encouraged.  Examples are given below, but applications are not limited
to these areas of research:

*       Epidemiological studies to determine the prevalence of
post-polio syndrome and to develop standardized diagnostic criteria.

*       Pathogenic studies emphasizing the relative stability of
reinnervation following infection with the polio virus, terminal
sprouting, and growth factors.

*       Animal models to study the pathogenesis of the original insult,
reinnervation, possible reappearance of symptoms and restoration of
function.

*       Use of new molecular biological techniques such as cloned
polio cDNAs and the polymerase chain reaction (PCR) to detect the polio
virus.

*       Development of strategies of immunotherapy if it is determined
that an autoimmune mechanism is involved.

*       Development of therapeutic strategies to improve or restore
neuromuscular function.

STUDY POPULATIONS

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 must 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 exclude or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear compelling
rationale must 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 must 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 must be provided.

For the purpose of this policy, clinical research is defined as 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
review will be deferred until the information is provided.

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.

APPLICATION PROCEDURES

Applications must be submitted on the grant application form PHS 398
according to instructions contained in the application kit.
Applications submitted after May 1, 1992, are to use the 9/91 revision
of the form PHS 398.  Application kits are available from most
institutional business offices and may be obtained from the Office of
Grants Inquires, Division of Research Grants, Westwood Building, Room
449, National Institutes of Health, Bethesda, MD 20892, telephone
301-496-7441.

Check "yes" in item two on the face page of the application and type
"Post-Polio Syndrome, PA-92-40."

Applicants for the P01 or P50 must use the application format as
described in the NINDS pamphlet, "Application Guidelines:  Program
Project and Clinical Research Center Grants," that may be obtained from
the contacts listed under INQUIRIES.

Deadlines for the receipt of applications are February 1, June 1, and
October 1.  The completed original application and six legible copies must
sent or delivered to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892

REVIEW PROCEDURES

Applications will be assigned on the basis of established Public Health
Service referral guidelines.  Applications will be judged on  scientific
merit and program relevance in accordance with NIH policy and procedures
involving peer review.  An initial review will be made by an appropriate
study section of the Division of Research Grants for research grants and
FIRST awards and by an appropriate institute committee for program
projects and centers.  A second level of review will be made by an
appropriate national advisory council.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications.  The following will be used in making funding decisions:

*       Quality of the proposed project as determined by peer review
*       Availability of funds
*       Program balance among research areas of the announcement

INQUIRIES

For further information regarding this announcement, potential
applicants may write or call:


Paul L. Nichols, Ph.D.
Developmental Neurology Branch
Division of Developmental, Convulsive, and Neuromuscular Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 8008
Bethesda, MD 20892
Telephone:  (301) 496-5821

For fiscal and administrative inquires regarding this announcement,
potential applicants may write or call:

Dwight H. Mowery, Jr.
Grants Management Specialist
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD 20892
Telephone:  (301) 496-9231

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.853 Clinical Research Related Neurological Disorders and 93.854
Biological Basis Research in the Neurosciences.  Awards are made under
authorization of the Public Health Service Act, Title IV, part A (Public
Law 78-410, as amended by Public Law 99-150, 42 USC 241 and 285) and
administered under PHS grants policies and Federal Regulations 42 CFR
and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review.



