POST-POLIO SYNDROME ------------------- NIH GUIDE, Volume 21, Number 5, February 7, 1992 --------- 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.