NIH GUIDE, Volume 22, Number 9, March 5, 1993

PA NUMBER:  PA-93-062

P.T. 34


  Convulsive Disorders 



National Institute of Neurological Disorders and Stroke


The Division of Convulsive, Developmental, and Neuromuscular

Disorders, National Institute of Neurological Disorders and Stroke

(NINDS) encourages the submission of research grant applications

related to genetics of the epilepsies.  The NINDS solicits submission

of research project grants to stimulate research in both basic and

clinical aspects of genetics of the epilepsies.  The scope of this

program encompasses both animal and human studies which would utilize

a variety of experimental approaches and methods.

In 1980, the NINDS cosponsored a conference for discussion of the

epidemiologic, genetic, clinical and molecular strategies that could

be used to study the pathogenesis of epilepsy.  In the intervening

decade human genetics, and neurogenetics in particular, have evolved

at a remarkable pace.  In 1991, a second conference on genetics and

epilepsy critically reviewed a diversity of research strategies and

pointed the way for future research.

At the international conference, a number of areas that could profit

from research, including applications of new technologies to epilepsy

research, were identified.  The NINDS seeks to encourage cross-

communication among diverse scientific disciplines so that the

potential of all of the relevant neurosciences can be brought to bear

on the research problem of genetics of the epilepsies.


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 priorities.  This program

announcement, Research Grants Related to Genetics of the Epilepsies,

is related to the priority areas of the epilepsies.  Potential

applicants may obtain a copy of "Healthy People 2000" (Full Report:

Stock No. 017-001-00474-0, or Summary Report:  Stock No.

017-001-00473-0) through the Superintendent of Documents, Government

Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).


Applications may be submitted by foreign and domestic institutions,

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 are eligible for research project grants (R01)



The support mechanisms for grants in this area will be the

investigator-initiated research project grant (R01), the First

Independent Research Support and Transition (FIRST) award (R29), the

program project grant (P01), and the center grant (P50).  As

consistent with the aforementioned mechanisms, the Principal

Investigator or program director, as well as any participating

investigators, will plan, direct, and perform the research.

Applicants for program project grants should contact the NINDS

representatives listed below as early as possible in the planning



The intent of this program announcement is to increase understanding

of the role of genetic factors in human epilepsy.  Some examples of

areas of research interest are given below.  However, applications in

other areas related to the genetics of epilepsy are welcome.

Collaborative Studies.  Collaboration between molecular geneticists

and clinicians who have access to informative pedigrees is

encouraged.  Additional research to localize more precisely genetic

abnormalities associated with specific epilepsy syndromes is

encouraged.  Such studies may permit the identification of abnormal

gene products whose defect can be related to seizure activity.

Electrophysiological Studies.  There is some evidence that genetic

mutations, for reasons that are unclear, may affect the excitability

of individual neurons or neuronal nets. Therefore, research on

genetic influences on neural synchronization is appropriate.

Animal Models.  Genetic non-human animal models of epilepsy can be

particularly informative.  At the present time there is no model that

correlates with human temporal lobe epilepsy.  The development of

appropriate animal models may permit the identification of a genetic

defect responsible for reduced seizure threshold, not only in

idiopathic epilepsy, but those seizures associated with febrile

episodes or seizures after head trauma.

Genetic Susceptibility to Neuronal Damage Caused by Seizures.  There

is evidence that an initial seizure may predispose to subsequent

seizures in certain individuals by producing some alteration or

damage in structures controlling cortical excitability.  This

susceptibility may have a genetic basis, and highlights the need for

identification of particular genes whose products affect control of

excitability, leading some individuals to have recurrent seizures

after the initial one.




NIH policy is that applicants for NIH 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 that 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 or ethnic group. In addition, gender and

racial or 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

Sections 1-4 of the Research Plan AND summarized in Section 5, Human

Subjects.  Applicants are urged to assess carefully the feasibility

of including the broadest possible representation of minority groups;

however, the NIH recognizes that it may not be feasible or

appropriate in all research projects to include representation of the

full array of Unites States racial or ethnic minority populations:

Native Americans (including American Indians or Alaska Natives),

Asian or Pacific Islanders, Blacks, and 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 prevention 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 or ethnic minorities when it is important to apply the results

of the study broadly.  This directive should be addressed by


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' population, including


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 the NIH are

required to address these policies.  If the required information is

not contained within the application, the review will be deferred

until the information is provided. NIH funding components will not

award grants or cooperative agreements that do not comply with these



Applications are to be submitted on the grant application form PHS

398 (rev. 9/91) according to the instructions included in the

application package.  These application packages are available from

the office of sponsored research at most institutions eligible to

receive Federal grants and from the Office of Grants Inquiries,

Division of Research Grants, National Institutes of Health, Westwood

Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441.

Applicants for program project grants should request, from the

address below, a copy of the NINDS Guidelines:  Program Project and

Research Center Grants (rev. 06/92).  Receipt dates for new research

project grant applications and FIRST Awards (R01 and R29,

respectively) and for program project and center grant applications

(P01 and P50, respectively) are February 1, June 1, and October 1.

FIRST 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


On page 1 of form PHS 398, check "yes" in Item 2a, enter the number

of this Program Announcement in the space provided, and provide the

name of this Program Announcement ("Genetics of the Epilepsies") in

the blank space labeled "Title."

Submit a signed, typewritten original of the application, including

the Checklist and five exact photocopies for research project grant

and FIRST Award (R01, R29) applications or the original and three

photocopies if the application is for a program project or center

grant (P01, P50) to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**

If the application is for a program project or center grant (P01,

P50) an additional two copies of the form PHS 398 must be sent to the

address listed under INQUIRIES.


Research project grant applications and FIRST applications (R01 and

R29, respectively) will be reviewed for scientific and technical

merit by an appropriate study section in the Division of Research

Grants.  Program  project grant and center grant applications (P01

and P50, respectively) will be reviewed according to the practice of

the Institute to which the application is assigned.  The second level

of review will be by the appropriate National Advisory Council.


The standard review criteria will be used to assess the scientific

merit of applications.  Applications will compete for available funds

with all other applications. The following will be considered when

making funding decisions:

o  quality of the proposed projects as determined by peer review,

o  availability of funds, and

o  program balance among research areas.


Questions concerning scientific aspects of this Program Announcement

may be addressed to:

Charlotte B. McCutchen,  M.D.

Division of Convulsive, Developmental, and Neuromuscular Disorders

National Institute of Neurological Disorders

Federal Building, Room 114

7550 Wisconsin Avenue

Bethesda, MD  20892

Telephone:  (301) 496-1917

FAX:  (301) 496-9916

Questions concerning fiscal aspects of this Program Announcement may

be addressed to:

Patricia Driscoll

Grants Management Branch

National Institute of Neurological Disorders and Stroke

Federal Building, Room 1004

Bethesda, MD  20892

Telephone:  (301) 496-9231


This program is described in the Catalog of Federal Domestic

Assistance, Number 93.853, Clinical Research Related to Neurological

Disorders, and 93.854, Biological Basis Research in the

Neurosciences.  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 grants policies

and Federal Regulations 42 CFR Part 52 and 45 CFR 74.  This program

is not subject to the intergovernmental review requirements of

Executive Order 12372 or Health Services Agency review.


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