Funding News - NINDS Notes - October 2002

NINDS Invites Committee to Review t-PA Study Data

The NINDS recently invited an independent committee to review and consider the data from the five-year, multi-site “Tissue Plasminogen Activator for Acute Ischemic Stroke” study, published by the NINDS r-TPA Stroke Study Group in The New England Journal of Medicine, December 14, 1995. The study represents the first treatment for acute ischemic stroke, and the therapeutic agent t-PA was approved by the FDA for this usage in June of 1996.

In recent months, public debate about the study findings has resulted in some discussion within the medical community about the appropriate use of this treatment for stroke. In answer to this, the NINDS asked that the committee “address whether there is concern that eligible stroke patients may not benefit from rt-PA given according to the protocol used in the (NINDS) trials, and whether any subgroup imbalances invalidate the trial as claimed by some of the critics.”

The committee is chaired by W. Michael O’Fallon, Ph.D., professor of Biostatistics, former chair at the Department of Health Sciences Research at the Mayo Clinic, in Rochester, Minnesota, and a recent past president of the American Statistical Association. Dr. O’Fallon chose the members of the committee, who represent an international cadre of physician-scientists with expertise in biostatistics, clinical medicine, cerebrovascular disease, neurology, and emergency medicine. None of the committee members has a connection with the previous published study or with the manufacturer of t-PA. (See roster of the committee members below.)

The committee has full access to the study data, will re-analyze the study, and hopes to report its findings by early spring. The NINDS looks forward to the group’s findings and the presentation of the data analysis at professional meetings and in the scientific literature.

Committee Roster

W. Michael O'Fallon, Ph.D., Chair
Professor of Biostatistics
Mayo Clinic

Timothy J. Ingall, M.B. B.S., Ph.D.
Associate Professor of Neurology
Cerebrovascular Diseases Center
Mayo Clinic Scottsdale

Professor Thomas A. Louis, Ph.D.
Department of Biostatistics
Johns Hopkins Bloomberg School of Public Health

Lewis R. Goldfrank, M.D.
Director, Emergency Medicine
Bellevue Hospital Center
Professor, Clinical Medicine and Surgery
New York University School of Medicine

Kjell Asplund, M.D., Ph.D.
Head, Department of Medicine
University Hospital
Umea, Sweden

Vicki Stover Hertzberg, Ph.D.
Associate Professor
Department of Biostatistics
Emory University

NINDS-NIMH Microarray Consortium

The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) recently funded three medical research centers-creating the NINDS/NIMH Microarray Consortium-to broaden the scope of genetic research by studying the origins and behavior of brain diseases. The participating centers-Children’s National Medical Center in Washington, DC, Duke University in Durham, North Carolina, and the University of California in Los Angeles-received a total of $9 million from NINDS and NIMH.

The primary goal of the consortium, which will combine gene expression profiling resources from the three centers, is to advance translational research through acquisition and dissemination of high quality expression array data. Gene expression profiling makes use of the recently announced human genome sequence to visualize how genes interact with one another in an aberrant fashion to cause human diseases.

“The establishment of this consortium expands the possibility of identifying what genes are involved in certain brain diseases,” said Thomas Miller, Ph.D., program director in the NINDS Extramural Technology Development Program. “By pooling the genomic capabilities of the three centers and sharing findings through publicly accessible web sites, we increase the chance of finding viable cures and therapies for many debilitating illnesses.”

Each consortium center specializes in one of three microarray technologies-cDNA, oligonucleotide, or Affymetrix-which provide information about the genes turned on or off in the diseased tissues being studied. Scientists use these microarray technologies to compare genetic patterns between an individual with a disease and an unaffected person. Using this information, investigators hope to be able to identify the genes responsible for certain disorders so that treatments can be developed that have a direct impact on the disease mechanisms.

Using this state of the art technology, the consortium plans to unravel the molecular mechanisms involved in the multitude of brain diseases, including Alzheimer’s, autism, epilepsy, multiple sclerosis, Parkinson’s, Tourette syndrome, cerebral palsy, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder.

Data generated by the consortium will become publicly available six months after its initial generation so the entire scientific community can benefit from this publicly funded endeavor. The consortium will also encourage NINDS and NIMH grantees to visit one of the centers to learn the techniques involved in gene expression profiling.

For more information on the consortium visit the web site at: http://arrayconsortium.tgen.org.

NIMH and NINDS conduct and support the majority of the nation’s biomedical research on the brain. Both are components of the National Institutes of Health (NIH).

Research on the Causes and Mechanisms of Dystonia Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Eye Institute (NEI), the National Institute of Child Health and Human Development (NICHD), and the National Institute on Deafness and Other Communication Disorders (NIDCD) invite applications for research on the causes and mechanisms of dystonia.*

Dystonia is the third most common movement disorder, affecting more than 500,000 individuals in the United States. The disorder has many different causes. Some forms of dystonia are associated with specific genetic or environmental risk factors, but the underlying pathophysiological pathways remain elusive.

Examples of potential areas of interest include: identification of genetic factors and inheritable mechanisms associated with dystonia, including new gene discovery, causes of variable penetrance, multigene interactions, and studies of other potential molecularly based disease-modifying factors; identification of proteins that interact with dystonia-related cellular factors (genes, proteins) and determination of their coordinated function; creation and characterization of animal models for studying the pathophysiological basis of dystonia, functional consequences, and potential therapeutic strategies; determination of the role of environmental factors in inducing cellular/neurophysiological changes associated with dystonia and dystonia-related proteins; studies of abnormalities in both plasticity and motor learning mechanisms that are relevant to dystonias; development of improved diagnostic and prognostic techniques; studies of the epidemiology of primary and secondary dystonia; therapeutic strategies in primary and secondary dystonia including both pharmacological and non-pharmacological interventions; studies on assistive devices, orthotics, and potential accommodations; studies on environmental risks that cause or exacerbate dystonia; and studies on the features of pain in dystonia, including how treating pain may affect the underlying disability

For more information, potential applicants should contact Dr. Katrina Gwinn-Hardy, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2142, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-402-1501; e-mail: gwinnk@ninds.nih.gov .

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PA-02-156.html.

Applications for Collaborative Neurological Sciences Award Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), and the National Institute on Drug Abuse (NIDA) invite applications for the Collaborative Neurological Sciences Award.*

The purpose of the award is to encourage collaborative research among scientists at minority institutions and grantees from leading research laboratories that have NIH or equivalent grant support to conduct neuroscience research. The award will support a research project in which the applicant and collaborating neuroscientist(s) work in a clearly defined area of mutual research interest. The project should consist of a research plan that involves a collaborative effort among the participating investigators, each of whom will be conducting a portion of the total research project in his/her own laboratory. Examples of the collaborative interactions include sharing ideas and data, and exchanging research techniques and expertise.

Examples of potential areas of interest include: stroke and other cerebrovascular diseases and disorders; episodic neurological states, such as epilepsy, chronobiology, circadian rhythms, and sleep; tumors of the nervous system; demyelinating and immunologically mediated disorders of the nervous system; neuro-AIDS and other viral-associated diseases of the nervous system; neuropsychiatric aspects of HIV/AIDS; neuromuscular and peripheral nerve disorders; fundamental neural processes; sensory and motor processes; pain; neurodegenerative diseases and disorders; trauma and injury to the nervous system; repair and plasticity of the nervous system; behavioral and cognitive neuroscience, including language processing; neurogenetics; nervous system development; and neurological impacts associated with drugs of abuse and the medical/mental/biological consequences and co-morbidity related to chronic drug use.

For more information, potential applicants should contact Dr. Gayathri Jeyarasasingam, Program Director, Office of Minority Health and Research, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2149, Bethesda, MD 20892; telephone: 301-496-3102; fax: 301-594-5929; e-mail: gj62v@nih.gov .

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PAR-02-130.html.

Research on the Continued Development and Maintenance of Bioinformatics and Computational Biology Software Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites grant applications for research on the continued development and maintenance of bioinformatics and computational biology software. This announcement is made together with 9 other components of the National Institutes of Health (NIH).*

Biomedical research laboratories occasionally develop software to solve problems in the laboratory. These software packages sometimes evolve into well-designed systems that can be easily extended and are useful to communities much broader than the members of the originating laboratory.

The goal of this program announcement (PA) is to support the continued development, maintenance, testing and, evaluation of pre-existing bioinformatics/computational biology software for data management and analysis, computational biology, and modeling and simulation. The proposed software should not substantially duplicate another software package that is already in wide use. This PA pertains to bioinformatics/computational biology software that performs an important function in furthering biomedical research. The software should be reliable and precise according to the computing demands of end-users. The algorithms used by the software should be well-documented, as should be the underlying assumptions of these algorithms to prevent potential misuse. Contemporary software must be fully documented and easy to modify and extend. Defects that arise in any software must be correctable with limited effort.

For more information, potential applicants should contact Dr. Yuan Liu, Program Director, Channels, Synapses, and Circuits Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2110, Bethesda, MD 20892; telephone: 301-496-1917; fax: 301-480-2424; e-mail: liuyuan2@ninds.nih.gov.

*For a full list of supporting NIH components and a more detailed description of this program announcement, please visit the NIH web site at: http://grants2.nih.gov/grants/guide/pa-files/PA-02-141.html.

Research on the Genetic Variation and Architecture of Complex Phenotypes Sought

The National Institute of Neurological Disorders and Stroke (NINDS) encourages grant applications for research on the genetic variation and architecture of complex phenotypes.*

Complex phenotypes are those that exhibit familial clustering. They may be continuous in distribution, like height or blood pressure, or they may be dichotomous, like affected and not affected. Genetic architecture refers to the full range of genetic effects on a trait. It is less a fixed property of the phenotype than a characteristic of a phenotype in a particular population, and it changes according to gene and genotype frequencies, distributions of environmental factors, and such biological properties as age and sex.

Areas of potential research interest include: variation in basic biological systems, including sequences, structures, and pathways that direct metabolism and development; variation in these systems within individuals, and among individuals, populations, and species with the goal of learning how these complex systems interact and evolve; determination of the extent to which genetic architecture is shared across populations and among species; effects of admixture, population history, recombination, mutation, population structure, selection, and drift on the organization of variation; collection and analysis of both new and existing data; tools and models for identifying and measuring important contextual features; and measuring the impact of context on biological data.

For more information, potential applicants should contact Dr. Katrina Gwinn-Hardy, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2142, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-402-1501; e-mail: gwinnk@ninds.nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PA-02-110.html.

Research on Increasing Quality of Life in Mobility Disorders Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Nursing Research (NINR), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Institute of Child Health and Human Development (NICHD) invite grant applications for research on increasing quality of life for individuals living with mobility-limiting disorders.*

Conditions that limit mobility include multiple sclerosis, Parkinson’s disease, stroke, traumatic brain or spine injuries, congenital abnormalities, obesity, arthritis, lower limb ischemia, and lung and balance disorders. There has been limited research on the psychosocial effects and quality of life experienced by people with these conditions. In addition to limited mobility, symptoms of pain and fatigue are common and may have a negative effect on psychosocial and physical functioning. Strategies to improve coping with symptoms of mobility-limiting conditions may improve quality of life for these individuals.

Areas of potential research interest include studies to: identify unique interventions to maintain physical functioning in challenging populations such as cognitively impaired older adults with limited mobility; identify strategies to improve quality of life and psychosocial adjustment in individuals with limited mobility; develop strategies to minimize the secondary symptoms of pain and fatigue that may be found in persons with limited mobility; explore whether gender and racial/ethnic influences occur in response to the physical and psychosocial functioning in persons with limited mobility; develop and test interventions to address the fear of functional dependence and reduce the need for relying upon others for accomplishing the activities of daily living; determine the factors contributing to quality of life and positive outcomes for individuals experiencing a mobility disorder; determine factors associated with successful adaptation to a sudden decrease in mobility; identify barriers to maximum physical and psychosocial functioning in persons with limited mobility; identify unique factors that promote quality of life in people who have limited mobility secondary to conditions such as lung disease and obesity; and evaluate the impact on psychosocial functioning or quality of life of the use of assistive devices or neural prostheses in managing limited mobility.

For more information, potential applicants should contact Dr. Daofen Chen, Program Director, Channels, Synapses, and Circuits Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2131, Bethesda, MD 20892; telephone: 301-496-1917; fax: 301-402-1501; e-mail: daofen_chen@nih.gov.

*For more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PA-02-111.html.

Applications for Novel Approaches to Enhance Animal Stem Cell Research Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites grant applications for novel approaches to enhance animal stem cell research. This announcement is made together with 11 other components of the National Institutes of Health (NIH).*

Stem cells are valuable research models for studying biological and disease processes, and for creating disease models. These cells also hold promise as model systems for developing therapeutics and replacement tissues through understanding of control of cellular differentiation. Thus far, embryonic stem cells have been isolated from some biomedically important nonhuman research models. In addition, stem cells with a more restricted potential have been characterized from post-embryonic tissue types. However, research is needed to provide a full array of totipotent and multipotent stem cells from nonhuman biomedical research animal models, as well as to provide the research tools to identify, characterize, and purify those cells.

Areas of potential research interest include studies to: expand the number of nonhuman animal model systems in which embryonic stem cells are available; identify, isolate, culture, and characterize multipotent stem cell populations derived from nonhuman embryonic stem cells and from post-fetal tissue types; generate and use panels of markers for stem cell attributes common across species for use in characterization and isolation of stem cells in a range of animal species or tissues; and create universal methods of culture to maintain the undifferentiated state of embryonic or other characterized, multipotential stem cells across nonhuman animal species.

For more information, potential applicants should contact Dr. Arlene Chiu, Program Director, Repair and Plasticity Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2206, Bethesda, MD 20892; telephone: 301-496-1447; fax: 301-480-1080; e-mail: chiua@ninds.nih.gov.

*For a full listing of supporting NIH components and a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PA-02-147.html.

Research on the Pathogenesis and Treatment of Dyskinesias in Parkinson’s Disease Sought

The National Institute of Neurological Disorders and Stroke invites grant applications for research on the development and treatment of dopamine-induced dyskinesias in Parkinson’s disease.*

Dyskinesias are a major complication of the treatment of PD. More than half of all persons treated with levodopa-the standard therapy for PD-or other dopaminergic agonists subsequently develop dyskinesias. In many cases these treatment-induced complications limit the amount of drug that can be administered and, as a result, limit symptom relief. Clinical presentations of dyskinesias vary significantly. When severe or painful, they limit therapy but when mild they can be well-tolerated by patients. However, even when mild, it is widely held that the appearance of dyskinesias foreshadows the development of other, more disabling motor complications. Therefore even mild dyskinesias may lead the treating physician to reduce therapy-at a price of increased rigidity for the patient. The pathogenesis of dyskinesias is poorly understood.

Examples of potential research areas of interest include: physiological and functional imaging studies in MPTP-treated primates followed by molecular neuroanatomy to establish the altered circuitry of dyskinesia; intraoperative recordings from humans during surgery to alleviate dyskinesias; pre-clinical studies of non-dopaminergic agents in dyskinetic primates; development and validation of clinical tools such as a dyskinesia rating scale or a predictor of motor complications; and pilot studies of non-dopaminergic agents in dyskinetic parkinsonian patients.

For more information, potential applicants should contact Dr. Paul Sheehy, Program Director, Neurodegeneration Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2214, Bethesda, MD 20892; telephone: 301-496-5680; fax: 301-480-1080; e-mail: sheehyp@ninds.nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PAS-02-129.html.

Research on Precursor Cells in Skeletal Muscle Repair and Hypertrophy Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), and the National Institute of Child Health and Human Development (NICHD) encourage grant applications for research to isolate, characterize, and identify the precursor cells involved in skeletal muscle growth and repair.*

Mammalian muscle contains a set of cells capable of regeneration and repair. These regenerative cells play an important role in the growth of postnatal muscle, with skeletal muscle representing 40-50 percent of the weight of adults. An important question in muscle development and muscle repair is the origin of these cells and their relationship to stem cells that circulate within the blood.

Potential areas of research interest include: projects to identify, isolate, culture, and characterize cells that are precursors of muscle growth or regeneration; projects to generate and use panels of markers for use in characterization and isolation of skeletal muscle precursor cells; studies to determine the origins and fates of muscle precursor cells; characterization of differences between skeletal muscle cells and other muscle precursor cells derived from muscle; research on mechanisms governing the role of muscle precursor cells in muscle plasticity, adaptation, and aging; characterization of biological functions of muscle precursor cells; projects to create methods of culture to maintain muscle precursor cells in stages when they proliferate; studies to clarify the mechanisms of muscle precursor cell differentiation; research to develop and optimize methodologies for directing the differentiation of muscle precursor cell populations; applying muscle precursor cell therapies to muscle diseases and disuse muscle atrophy or wasting (also called sarcopenia); and use of precursor cells in the context of exercise, functional electrical stimulation, or other therapeutic strategies.

For more information, potential applicants should contact Dr. Giovanna Spinella, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2132, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-401-1501; e-mail: gs41b@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PA-02-136.html.

Research on Racial/Ethnic Disparities in the Incidence of Diabetes Complications Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Eye Institute (NEI), the National Institute of Nursing Research (NINR), and the National Heart, Lung, and Blood Institute (NHLBI) invite grant applications for research studies to understand racial/ethnic disparities in the development of the micro- and macrovascular complications of diabetes.*

Racial and ethnic groups differ considerably in the frequency of diabetes in their populations. Microvascular complications of diabetes such as nephropathy, retinopathy, and neuropathy are a major problem among Native Americans, African Americans, Hispanic Americans, and Asian and Pacific Islanders. In contrast, racial and ethnic minorities with diabetes often have lower rates of macrovascular disease including cardiovascular disease and stroke than Caucasians. The reasons for these differences are not well understood.

Potential areas of research interest include studies to: determine the rates of micro- and macrovascular diabetic complications in appropriate representative samples of contemporary populations; identify genes which might affect the development and progression of micro- and macrovascular complications in different populations; determine whether there are differences in metabolism, insulin sensitivity, energy expenditure, beta cell function, and body composition that might influence glycemic control and risk of complications in different populations; compare the contribution of glycemia versus other risk factors in the development of micro- and macrovascular disease in patients with diabetes, and study how treatment of these factors may influence rates of development of complications in different racial/ethnic groups; investigate environmental factors, such as medical care, behavior and lifestyle, and socioeconomic status, that may contribute to risk for development and progression of complications; and determine whether different pathophysiological mechanisms or risk factors are operative among subgroups within racial/ethnic minorities.

For more information, potential applicants should contact Dr. Paul Nichols, Program Director, Systems and Cognitive Neuroscience Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2118, Bethesda, MD 20892; telephone: 301-496-9964; fax: 301-401-2060; e-mail: pn13w@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PA-02-165.html.

Grant Applications to Develop Tools for Genetic Studies in Zebrafish Sought

The National Institute of Neurological Disorders and Stroke (NINDS) encourages grant applications to develop tools for genetic studies in zebrafish. This announcement is made together with 17 other components of the National Institutes of Health (NIH).*

As a vertebrate, the zebrafish is more closely related to humans than are yeast, worms, or flies, and has a number of advantageous features as a model organism for study of vertebrate development, disease, and biological pathways. The most powerful and unique feature of the zebrafish is that it is a vertebrate model organism with a proven track record of easily executed, large-scale forward mutagenesis screens. There are few tools for targeted gene knockout, conditional gene expression, enhancer trapping, or rapid insertional mutagenesis. The goals of this program announcement are to develop new genetic tools and identify additional mutants. More efficient tools will make screens easier and the discovery of mutants affecting important processes will stimulate additional research on methods to study those mutants.

Areas of potential research interest include: development and/or application of novel methods of mutagenesis; development of systems for rapid mapping or identification of point mutations; and development of technology for gene inactivation and gene expression manipulation. Also of interest is the development and/or application of novel screens for mutants including: phenotypic screens based on observation of alterations in morphology, physiology, or behavior; genetic screens focusing on identifying mutations that affect the structure and function of specific tissue/organ systems; screens focusing on identifying novel developmental genes and pathways, including those mediating sensitivity or resistance to environmental teratogens; screens to analyze the genetic basis of adult phenotypes including behavior, aging, organ disease, cancer, and responses to environmental toxins, alcohol, and drugs of abuse; and sensitized screens, using strains carrying a known mutation, in order to identify extragenic suppressors or enhancers of that mutation.

For more information, potential applicants should contact Dr. Danilo Tagle, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2133, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-401-1501; e-mail: tagled@ninds.nih.gov.

*For a full list of supporting NIH components and a more detailed description of this program announcement, please visit the NIH web site at: http://grants2.nih.gov/grants/guide/pa-files/PAR-02-142.html.

Translational Research: Exploratory/Developmental Projects Sought

The National Institute of Neurological Disorders and Stroke (NINDS) encourages grant applications for exploratory or developmental translational research projects that focus on neurological disorders.*

Translational research is the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. Remarkable insights have been made recently in the molecular, genetic, and cellular bases of neurological disease. In many cases, developmental work must be completed before the basic research results can be translated into effective therapies. A key requirement for successful therapeutic development is the characterization of new assays, models, tools, and technologies that provide for reliable discovery and testing of therapeutic approaches. The purpose of this announcement is to encourage projects that provide tools and resources for therapy development.

Examples of potential research topics of interest include: identification of targets for therapeutic intervention; development of assays that permit the preliminary screening of candidate therapeutics; development of animal models that permit further evaluation of candidate therapeutics and/or toxicology studies; development of tools and technologies that can be directly used for therapy development; and preliminary identification of candidate therapeutics that can be evaluated through further preclinical testing.

For more information, potential applicants should contact Dr. Thomas Miller, Program Director, Technology Development Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2139, Bethesda, MD 20892; telephone: 301-496-1779; fax: 301-402-1501; e-mail: 208y@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PAR-02-138.html.

Translational Research: NINDS Cooperative Program Applications Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites applications for the NINDS Cooperative Program in translational research.*

Translational research is the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. This program includes only activities directly focused on therapy development necessary to begin clinical testing. Projects will typically include either an assay that has demonstrated relevance to a neurological disorder or candidate therapeutics that have a significant effect in a disease model.

The NINDS Cooperative Program in Translational Research is implemented through three coordinated cooperative agreement mechanisms: 1.) Translational research conferences are used flexibly to meet the needs of research communities with translational research efforts at different stages of development. All meetings must have a translational research focus and be directly relevant to a clinical intervention for a neurological disorder; 2.) Single-component translational research projects focus on a single problem or approach in therapy development for a neurological disorder. The research is focused on a neurological disorder or a group of closely related neurological disorders; and 3.) Multi-component translation research projects support research programs that take a multidimensional or comprehensive approach to therapy development. These projects support interdisciplinary teams of investigators who are dedicated to translational research focused on a neurological disorder or a group of closely related neurological disorders.

For more information, potential applicants should contact Dr. Thomas Miller, Program Director, Technology Development Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2139, Bethesda, MD 20892; telephone: 301-496-1779; fax: 301-402-1501; e-mail: tm208y@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PAR-05-158.html.

Mentored Research Scientist Development Awards in Translational Research Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites applications for Mentored Research Scientist Development Awards in Translational Research.*

The goal of this program announcement is to provide a career development opportunity for new investigators to build a program of translational research in neurological disorders under the guidance of an experienced mentor. The overall objective of this program is to attract and encourage investigators at the postdoctoral or early faculty development stage to focus their efforts on translational research in neurological disorders. This program is intended to promote more extensive interaction among basic and clinical researchers, and to accelerate the development of interventions and effective treatments that will improve the quality of life of persons with neurological disorders.

Translational research is the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. The career development and training experience must focus on translational research, and should include the principles of therapeutics, candidate screening and evaluation, assay validation, development and use of animal models of neurological disorders, toxicology and safety testing, biostatistics, preparation of investigational new drug (IND) or investigational device exemptions (IDE) applications, and interactions with private sector companies involved in the manufacture and marketing of therapeutic drugs or devices. Although all of these elements normally will not be included in the research project, experience and training in these areas should be built into the career development plan.

For more information, potential applicants should contact Dr. Henry Khachaturian, Training, Career Development, and Referral Officer, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2154, Bethesda, MD 20892; telephone: 301-496-4188; fax: 301-594-5929; e-mail: hk11b@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/pa-files/PAR-02-140.html.

Applications for Muscular Dystrophy Cooperative Research Centers Requested

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Institute of Child Health and Human Development (NICHD) request applications to establish Muscular Dystrophy Cooperative Research Centers to increase basic and clinical research on all forms of muscular dystrophy (MD).*

The primary goal of this request for applications (RFA) is to create research centers that will bring together expertise, intrastructure, and resources focused on the major questions about MD. MD refers to a group of genetic disorders characterized by progressive weakness and wasting of muscles. Although research has revealed much about the genetic defects associated with many forms of MD, treatment for these diseases has not changed significantly. Scientists need to learn more about the pathogenesis of the diseases to improve early detection and screening, diagnosis, treatment, and prevention of these disorders.

Potential areas of research interest include studies to: examine pathogenic mechanisms leading from gene defects to MD phenotypes; clarify the role of inflammatory changes that accompany tissue degeneration (e.g., explore the relationship between inflammatory cells, muscle cell death, and blood vessels); clarify relationships between genotype and natural history of disease; develop improved outcome measures and methods to monitor changes due to treatment or disease progression; examine the involvement of apoptotic cell death in the process of muscle fiber degeneration; develop methods and procedures, such as enhanced imaging that will provide for better monitoring of disease processes; examine genetic heterogeneity and search for additional candidate genes; examine genotype/phenotype correlations within and between families; determine if the dystrophin-glycoprotein complex has both a mechanical and signaling role; analyze properties of muscle cells derived from affected tissue; determine basis of differential involvement of muscles, reflected by the regional pattern of disease; and pursue the development and sharing of appropriate animal models for MD.

APPLICATION RECEIPT DATE: February 24, 2003.

For more information, potential applicants should contact Dr. Giovanna Spinella, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2132, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-401-1501; e-mail: gs41b@nih.gov.

*For a more detailed description of this RFA, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/rfa-files/RFA-AR-03-001.html.

Applications for Neuroscience Scholars Program Requested

The National Institute of Neurological Disorders and Stroke (NINDS) requests applications for the Neuroscience Scholars Program.*

The purpose of the program is to enable the grantee organization to provide research and related experiences for undergraduate, graduate and medical students, postdoctoral fellows, and other junior scientists from minority groups to broaden their skills and enhance their career development. This request for applications (RFA) will support innovative education programs that provide minority neuroscientists within scientific and/or professional societies and organizations with enhanced research and training activities to strengthen their career potential.

The education programs may include: travel awards to permit attendance at relevant national meetings and important seminars in their research area; travel awards for scholars to participate in brief research training and career development opportunities in the extramural neuroscience community; tuition and travel awards to summer workshops; development or enhancement of opportunities for students and young scientists to establish mentor relationships with prominent neuroscience investigators; visiting tours for graduate students from minority institutions to meet faculty at various institutions; leadership workshops; scientific retreats organized by and for students; rotations with journal publishers to gain insight into scientific publication processes at the editorial/review level; workshops to train mentors; cultural sensitivity training; and development of web-based mentoring tools.

APPLICATION RECEIPT DATE: November 21, 2002.

For more information, potential applicants should contact Dr. Gayathri Jeyarasasingam, Program Director, Office of Minority Health and Research, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2149, Bethesda, MD 20892; telephone: 301-496-3102; fax: 301-594-5929; e-mail: gj62v@nih.gov.

*For a more detailed description of this RFA, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/rfa-files/RFA-MH-03-002.html.

Applications on Stigma and Global Health Research Program Requested

The National Institute of Neurological Disorders and Stroke (NINDS) requests applications for research on the role of stigma in health, and on how to prevent or mitigate its negative effects on the health and welfare of individuals, groups, and societies worldwide. This announcement is made together with 12 other components of the National Institutes of Health (NIH) and the Canadian Institutes of Health Research (CIHR)/Institute of Neurosciences Mental Health and Addiction (INMHA) with the International Development Research Center (IDRC).*

The goals of this request for applications (RFA) are to encourage research across a variety of scientific disciplines including the biomedical, social, and behavioral sciences; to clarify the cause of stigma in public health; and to develop and test interventions to lessen the negative effects of stigma on health outcomes.

Areas of potential research interest include: the role of stigma in specific public health problems, diseases, or disorders, and its implications for issues from etiology to interventions and public policy; the implications of stigma for access to care and treatment, and how stigma affects outcomes across health conditions; systematic studies to determine psychological, social, economic, cultural, and political factors that operate in the creation of stigma and how they link to stereotypes, discrimination, and mistreatment in the context of health problems and health care systems; development of tools to study and document stigma and its impact on accurate determination of incidence and prevalence of health conditions, and to estimate the risk for over- or under-diagnosis as a result of stigma-related influences; evaluation of which interventions work for stigma-related health problems, the characteristics of successful interventions that can be scaled up or generalized to other stigmatized public health problems and/or to other populations and cultures; the role of disclosure of disease in an individual's personal or professional life and its relationship to perceived stigma; and identification of methods to minimize (or eliminate) the consequences of stigma/stigmatization on the recognition and diagnosis of health conditions and on options for treatment and/or rehabilitation.

APPLICATION RECEIPT DATE: November 14, 2002.

For more information, potential applicants should contact Margaret Jacobs, Program Director, Channels, Synapses, and Circuits Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2138, Bethesda, MD 20892; telephone: 301-496-1917; fax: 301-480-2424; e-mail: mj22o@nih.gov.

*For a full list of supporting NIH components and a more detailed description of this RFA, please visit the NIH web site at: http://grants1.nih.gov/grants/guide/rfa-files/RFA-TW-03-001.html.

Children with Fabry Disease Sought for Study

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) seek children with Fabry disease for a study to find out the extent of clinical and quality of life problems that affect boys or symptomatic girls with Fabry disease. The information gathered will serve to construct a trial of enzyme replacement therapy in the future.

The study includes a physical examination, and routine blood, urine, and other standard medical tests. Eligible boys are 6 to 17 years of age with Fabry disease. Eligible girls are symptomatic carriers of the same age. Children with additional illnesses such as cancer or diabetes will not be eligible.

The study will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. All study-related expenses will be paid by the NIH. The study is carried out in compliance with testing and safety standards of U.S. Department of Health and Human Services.

For more information, contact Connie Kreps, RN, or Dr. Raphael Schiffmann, NINDS, NIH, Building 10, Room 3D03, 10 Center Drive MSC 1260, Bethesda, MD 20892-1260, telephone: 301-496-1465, 1-800-258-0299 (toll-free), or 301-496-1465; fax: 301-480-8354; e-mail: ck41e@nih.gov or rs4e@nih.gov.

Persons with Neuronopathic Gaucher Disease Sought for Study

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) seek adults and children 12 years of age or older with neuronopathic Gaucher disease who are currently being treated with enzyme replacement therapy for a study of an investigational oral treatment for the disorder. It is hoped that this drug will be an effective treatment for the neurological symptoms of this disease.

Individuals will be screened to determine eligibility. Initially, the duration of the study will be 12 months. Eligible persons will be required to visit the clinic at regular 3-month intervals. The study will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. All study-related expenses will be paid by the NIH.

For more information, physicians should contact Dr. Raphael Schiffmann, NINDS, NIH, Building 10, Room 3D03, 10 Center Drive MSC 1260, Bethesda, MD 20892-1260, telephone: 301-496-1465 or 1-800-258-0299 (toll-free); fax: 301-480-8354.

Persons with Parkinson’s Disease Sought for Study

Investigators at the National Institute of Neurological Disorders and Stroke (NINDS) seek persons with Parkinson’s disease for a research study. The study will determine if the experimental drug JP-1730, when compared to a placebo, will help control both the symptoms of Parkinson’s disease and the complications of long-term treatment.

Eligible participants are those who find standard medications to be less effective than before, are 30 to 80 years of age, and are experiencing abnormal involuntary movements (dyskinesias). Persons with heart or lung disease, and those who are pregnant or breast feeding, will not be eligible.

The study, which lasts approximately 5 weeks and involves a short inpatient stay each week, will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. All study-related expenses will be paid by the NIH. This study is conducted under safety and testing standards of the Department of Health and Human Services.

To refer eligible patients, physicians should send a letter of referral and case summary to Dr. Thomas Chase, Chief, Experimental Therapeutics Branch, NINDS, NIH, Building 10, Room 5C106, 10 Center Drive MSC 1406, Bethesda, MD 20892-1406; fax: 301-496-6609. Please call Deserea Russell with any questions at 301-496-4604 or 1-800-362-3479. Refer to study number: 02-N-0236.

Persons with Progressive Supranuclear Palsy Sought for Study

Researchers at the National Institute of Neurological Disorders and Stroke (NINDS) are seeking people with progressive supranuclear palsy (PSP) for a study. The study will evaluate the safety and effectiveness of increasing doses of an experimental drug-recombinant-methionyl human glial cell line-derived neurotrophic factor (GDNF)-administered through an implanted pump and catheter system.

Eligible persons are those who have been diagnosed with mild to moderate PSP, are otherwise healthy and between the ages of 35 and 75, and who have a caregiver who can serve as their Durable Power of Attorney for Health Care. Persons not eligible for the study are those who have had a stroke or significant head trauma in the past two years, or have advanced PSP or clinically significant psychosis or hallucinations. Also ineligible are persons who are taking any antiparkinsonian medications that they or their doctors feel cannot be stopped, or those who have a known allergy to E. coli-derived products or a history of severe breathing difficulty after taking any medication, have an existing shunt or catheter system in their head, or have any other serious medical condition such as severe degenerative arthritis, cardiovascular disease, body weight less than 15 percent of ideal, or significant laboratory abnormalities that would interfere with assessment of the safety and effectiveness of the medication.

Participants in the study will have a catheter inserted directly into their brains. This is an ongoing study that will require participants to come to NIH every two to four weeks until the study concludes. Participation will last at least 2 years.

The study will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. All study-related expenses will be paid by the NIH. This study is conducted under safety and testing standards of the Department of Health and Human Services.

To refer eligible patients, physicians should send a letter of referral and case summary to Dr. Thomas Chase, Chief, Experimental Therapeutics Branch, NINDS, NIH, Building 10, Room 5C106, 10 Center Drive MSC 1406, Bethesda, MD 20892-1406; fax: (301) 496-6609. Please call Amy Bridgeman with any questions at 301-496-4604 or 1-800-362-3479. Refer to study number: 00-N-0145.

Persons with Spasmodic Dysphonia Sought for Research Studies

Investigators at the National Institute of Neurological Disorders and Stroke (NINDS) are seeking persons affected with adductor or abductor spasmodic dysphonia to participate in research studies to improve understanding of the physiological basis for these disorders.

Some studies are part of an overall effort to determine the role of sensory feedback from the larynx to the brain in the generation of voice breaks. Different methods are being used to evaluate the role of laryngeal sensation in symptom generation. Additional studies use non-invasive techniques for measuring speech physiology in abductor spasmodic dysphonia and include assessment of a new treatment approach for this disorder.

Eligible participants must be between 18 and 70 years of age and have either adductor or abductor spasmodic dysphonia or muscular tension dysphonia. Participants should be without a history of cardiac problems, asthma, or pulmonary disease. They must not be currently receiving treatment for their voice disorder and cannot have had treatment during the previous 4 months.

The studies will be conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. All study-related expenses will be paid by the NIH. The studies will be carried out under testing and safety standards of the Department of Health and Human Services.

For more information, interested persons may contact Dr. Christy Ludlow and their physicians should send a referral letter and a copy of their recent medical records to Dr. Ludlow, NINDS, NIH, Building 10, Room 5D38, 10 Center Drive MSC 1416, Bethesda, MD 20892-1416; telephone: 301-496-9366; fax: 301-480-0803; e-mail: Ludlowc@ninds.nih.gov.