Full Text PA-96-065
 
NEURONAL CEROID LIPOFUSCINOSIS, INCLUDING BATTEN DISEASE
 
NIH GUIDE, Volume 25, Number 23, July 12, 1996
 
PA NUMBER:  PA-96-065
 
P.T. 34

Keywords: 
  Neurological Disorders 

 
National Institute of Neurological Disorders and Stroke
 
PURPOSE
 
The National Institute of Neurological Disorders and Stroke announces
the reissuance of a program announcement (PA) (originally published
December 20, 1991) to notify the scientific community of its
continued interest in the submission of research grant applications
concerning neuronal ceroid lipofuscinosis.
 
HEALTHY PEOPLE 2000
 
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 PA,
Neuronal Ceroid Lipofuscinosis, Including Batten Disease, is related
to the priority areas of chronic disabling conditions and maternal
and child health.  Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report:  Stock No.017-001-11474-0 or Summary
Report:  Stock No.017-001-11473-1) through the Superintendent of
Documents, Government Printing Office, Washington, DC 20402-9325
(telephone 202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, 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.
Foreign institutions or organizations in foreign countries are not
eligible for First Independent Research Support Transitions (FIRST)
(R29) awards, program project grants (P01), or clinical center grants
(P50).
 
MECHANISM OF SUPPORT
 
The support mechanisms for grants in this area will be the individual
investigator-initiated research project grant (R01), FIRST (R29)
award, program project grant (P01), and clinical center grant (P50).
 
RESEARCH OBJECTIVES
 
The neuronal ceroid lipofuscinoses are a group of hereditary
neurodegenerative diseases in children and adults in which there is a
progressive loss of vision, seizures, and psychomotor degeneration.
There are three major forms of the disease in children, and one in
adults.  The common mode of inheritance is autosomal recessive, and
the general incidence in children is approximately 1.2 per 100,000
births.  The three main forms of childhood NCL are delineated based
on the age of onset, clinical course, and morphological observations.
At least 15 atypical variants have been described.
 
With the discovery of genes for two forms of the NCLs, infantile NCL
and juvenile NCL, the question of the biochemical and genetic defects
can now be addressed.  Work also must continue to identify the gene
defects for late infantile and adult onset NCL.
 
Despite intensive research efforts, the biochemical defect(s) for the
NCLs have not yet been identified.  In the juvenile, late infantile,
and adult forms there is storage of subunit c of mitochondrial ATP
synthase.  In the infantile form, there is storage of saposins A and
D. There is an increase in dolichols in the urine and brain of the
patients.  There is also storage of other minor materials in all
forms of the disease.
 
NINDS encourages submission of quality research proposals to
delineate the clinical and genetic types of the NCLs, to characterize
the genetic and biochemical defects in INCL and JNCL, to identify and
localize the gene(s) responsible for LINCL and adult onset NCL, and
to develop measures for the prevention, early diagnosis and treatment
of these disorders.  Studies may encompass all aspects of the
neurobiology of the NCLs by a variety of current and innovative
experimental approaches and methods.  Multidisciplinary approaches
are encouraged.  Areas of interest include, but are not limited to
the following research disciplines.
 
Genetic studies should focus on the determination of the gene defects
for the INCL and JNCL genes.  These should include studies to
determine the function of the encoded protein, and should not be just
a cataloging of the mutations.  Information obtained in these studies
should be helpful in understanding the normal metabolism of the
protein, in addition to understanding its role in disease process in
the NCLs.  Studies to determine the chromosomal location and gene
identification for LINCL, adult onset NCL and other atypical variants
are encouraged.  For cases where an animal has been determined to be
a model for a specific variant of NCL, genetic studies to determine
the defective gene would be appropriate.
 
Biochemical studies should utilize state of the art techniques to
identify and quantify the structural and mechanistic biochemical
defects underlying the disease.  Studies may employ either human or
animal tissues.  However, animal studies must clearly state relevance
to the human diseases.
 
Studies to elucidate the biochemical and genetic abnormalities of the
NCLs can be done in appropriate animal models.  Current. animal
models available for study include sheep, dogs, and mice. It will be
important to demonstrate how these animals mimic the human condition.
In addition, with the discovery of the genes for the INCL and JNCL,
recombinant technology can be used to generate animal models by
creation of "knockout" and transgenic mice.
 
Studies directed at therapeutic interventions may be included. These
studies may involve pharmacological interventions, or may include
gene therapy.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
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 new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which was reprinted in the Federal
Register of March 28, 1994 (FR 59 14508-14513) to correct typesetting
and errors in the earlier publication, and reprinted in the NIH GUIDE
FOR GRANTS AND CONTRACTS of March 18,1994, Volume 23, Number I 1.
 
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
 
APPLICATION PROCEDURES
 
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 may be obtained from
the Office of Extramural Outreach and Information Resources, National
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD
20892-7910, telephone 301/435-0714, email:
ASKNIH@odrockm1.od.nih.gov.  FIRST (R29) award applications must
include at least three sealed letters of reference attached to the
face page of the original application.  FIRST applications submitted
without the required number of reference letters will be considered
incomplete and will be returned without review.  In addition, the PA
title, ("Neuronal Ceroid Lipofuscinosis, PA-96-065) must be typed on
line 2 of the face page of the application form and the yes box must
be marked.
 
Submit a signed typewritten original of the application, including
the checklist, and five signed photocopies, in one package to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for courier or express service)
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by the
DRG.  Incomplete applications will be returned to the applicant
without further consideration.
 
Applications that are complete will be evaluated for scientific and
technical merit by an appropriate peer review group convened in
accordance with NIH peer review procedures.  As part of the initial
merit review, all applications will receive a written critique and
may undergo a process in which only those applications deemed to have
the highest scientific merit, generally the top half of all
applications under review, will be discussed, assigned a priority
score, and receive a second level review by the appropriate national
advisory council or board.
 
Review Criteria
 
o  scientific, technical, or medical significance and originality of
proposed research;
 
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
 
o  qualifications and research experience of the Principal
Investigator and staff,
 
o  particularly, but not exclusively, in the area of the proposed
research;
 
o  availability of the resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research; and
 
o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The Initial review group will also examine the provisions for the
protection of human subjects and animal welfare and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other
applications assigned to that Institute.  The following will be
considered in making funding decisions:  quality of the proposed
project as determined by peer review and availability of funds.
 
INQUIRIES
 
Written and telephone inquiries concerning this PA are encouraged.
Applicants for program project grants or centers should request, from
the address below, a copy of the NINDS Guidelines:  Program Project
and Research Center Grants.  The opportunity to clarify any issues or
questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic issues to:
 
Judy A. Small, Ph.D.
Division of Convulsive, Developmental, and Neuromuscular Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 8CO4
7550 Wisconsin Avenue MSC 9165
Bethesda, MD  20892-9165
Telephone:  (301) 496-5821
FAX:  (301) 402-0887
Email:  jsl34h@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
King P. Bond, Jr.
Division of Extramural Activities
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
7550 Wisconsin Avenue MSC 9190
BETHESDA, MD  20892-9190
Telephone:  (301) 496-9231
FAX:  (301) 402-0219
Email:  kb33s @nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.853 and 93.854.  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 103227, 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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