Funding News - NINDS Notes - March 2005

R21 Grant Applications for Alzheimer’s Disease Drug Discovery Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), the National Institute of Mental Health (NIMH), and the Institute for the Study of Aging (ISOA) invite R21 grant applications for the discovery, development, and preclinical testing of drugs to prevent and treat the cognitive impairment and behavioral symptoms of Alzheimer's disease (AD).*

AD is one of the most persistent and devastating dementing disorders of old age because it eventually leads to a complete loss of memory and the ability to function independently. In AD, connections among nerve cells are lost and specific neuronal populations die or are compromised, and aberrant proteins are formed in brain regions associated with memory and other symptoms of AD such as agitation and psychosis. At present the few treatments that are currently approved by the Food and Drug Administration for AD have demonstrated only modest effects in modifying the clinical symptoms for relatively short periods, and none has shown a clear effect on disease progression. Examples of areas of research interest include, but are not limited to: design, synthesis, and preclinical testing of compounds directed toward altering, modifying, or regulating the neuronal mechanisms associated with AD; the isolation, identification, characterization, synthesis, and preclinical testing of promising naturally occurring products; and development of novel delivery systems to target compounds to the brain, e.g., gene vectors, stem cells and other cell-based approaches, and protein and peptide delivery systems. For more information, potential applicants should contact Dr. Diane Murphy, Program Director, Neurodegeneration Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2222, Bethesda, MD 20892; telephone: 301-496-5680; fax: 301-480-1080; e-mail: dm152o@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PAS-05-022.html.

Research on Axonal Damage in Multiple Sclerosis Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites grant applications for clinical and translational research on axonal damage in multiple sclerosis (MS).*

MS is the second most common neurological disorder leading to disability in young adults, surpassed only by trauma. The disease is characterized by chronic inflammation and demyelination of the central nervous system (CNS) that over time may result in neurodegeneration. While axonal damage and neuronal cell death are likely to be the major causes of disability in the later, progressive phase of MS, new evidence suggests that even at early stages severance of nerve axons may occur and lead to irreparable nerve damage. Currently available therapies do not appear to significantly reduce this tissue loss.

Potential areas of research interest include, but are not limited to, studies on: therapeutic strategies for interference with molecular signals blocking axonal repair such as CNS myelin-associated inhibitors and glial scar-associated inhibitors; strategies promoting axonal maintenance and repair in demyelinating disease via delivery of trophic factors or the manipulation of a dysregulated signaling environment; the effects of channel blockers on axonal regeneration; delivery systems to target neuroprotective and regenerative compounds to MS lesions; endogenous remyelination strategies that target recruitment, survival, and maturation of oligodendrocyte precursor cells; and exogenous strategies for the delivery of myelin-forming cells such as transplantation of stem cells, oligodendrocyte progenitors, olfactory ensheathing cells, neurospheres, and Schwann cells.

For more information, potential applicants should contact Dr. Ursula Utz, Program Director, Neural Enviornment Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2134, Bethesda, MD 20892; telephone: 301-496-1431; fax: 301-480-2424; e-mail: uu1p@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PAS-05-002.html.

Applications for Research on Chronic Fatigue Syndrome Sought

The National Institute of Neurological Disorders and Stroke (NINDS) encourages grant applications for research on the pathophysiology and treatment of chronic fatigue syndrome (CFS). This announcement is made together with 12 other components of the National Institutes of Health (NIH).*

CFS is a debilitating and complex syndrome that involves multiple body systems. It is characterized by profound fatigue that is not improved by bed rest and may be exacerbated or re-kindled by physical or mental activity. Neither a specific cause nor any specific diagnostic test has been identified for this illness. Research is needed to provide a better understanding of the prevalence, pathogenesis, and pathophysiology of CFS, with the goal of developing improved diagnostic and intervention strategies.

Potential areas of research interest include, but are not limited to, studies to: define the prevalence of the disorder and identify distinct subgroups; explore whether pathogenesis and pathophysiology differ relative to age, sex, developmental period, and racial/ethnic background; develop novel and objective biological markers for the diagnosis of CFS; explore the role of neuroimaging modalities in the diagnosis, treatment, and progression of CFS; identify environmental and other precipitants and geographic correlates of CFS; explore multi-systemic factors as precipitants to CFS symptoms; elucidate the factors/mechanisms that elicit chronic pain and inability to sustain physical exertion in CFS patients; examine the relationships between cognitive deficits and sleep disturbances or sleep disorders; examine the role of neuroendocrine and neuroimmune functions in CFS pathogenesis and pathophysiology; examine the role of oxidative stress in the pathogenesis of CFS and marginal nutritional deficiencies in the etiology of CFS; determine the effectiveness of currently prescribed pharmacological, behavioral, and other treatments used in CFS; and examine the role of self-medication with alcohol and illicit and prescription drugs in CFS patients.

For more information, potential applicants should contact Dr. Linda Porter, Program Director, Systems and Cognitive Neuroscience Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2113, Bethesda, MD 20892; telephone: 301-496-9964; fax: 301-402-2060; e-mail: lp216a@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://grants.nih.gov/grants/guide/pa-files/PA-05-030.html.

Research on HIV Infection of the Central Nervous System Encouraged

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) encourage grant applications for research on HIV infection of the central nervous system.*

The introduction of highly active anti-retroviral therapy (HAART) has resulted in significantly improved survival of AIDS patients and decreased incidence of HIV-associated dementia. However, the improved survival has resulted in increased cumulative prevalence of nervous system complications of AIDS. Extensive research is underway to better understand the underlying mechanisms of neuropathogenesis of HIV-1.

Areas of research interest include, but are not limited to: primary and secondary mechanisms of HIV-1 neuropathogenesis; viral and host genetics; molecular markers associated with HIV-induced nervous system disease; neuroimaging studies; therapeutics; and neuroAIDS research in resource-limited settings. For more information, potential applicants should contact Dr. Michael Nunn, Program Director, Neural Environment Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2118, Bethesda, MD 20892; telephone: 301-496-1431; fax: 301-480-2424; e-mail: mn52e@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PA-04-154.html.

Applications for Manufacturing Processes of Medical, Dental, and Biological Technologies Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) invite small business innovation research (SBIR) and small business technology transfer (STTR) grant applications for research on manufacturing biomedical products and implementing new technologies in medical care. This announcement is made together with 18 other components of the National Institutes of Health (NIH).*

New methods, procedures, measures, and controls are needed for manufacturing a broad range of biomedical technologies and products and for lowering manufacturing costs for existing and/or new processes. Research that can help contain and reduce health care costs and that can improve the cost effectiveness, quality, and accessibility of the health care system is also encouraged.

Research topics of interest include, but are not limited to: flexible computer-assisted integrated manufacturing equipment and intelligent processing equipment adaptable to the varied needs of biomedical research and medical care device and material production; technology for manufacturing research instruments; technology for manufacturing clinical diagnostic devices and reagents; technology for manufacturing and delivering therapeutic drugs; technology for manufacturing implantable devices and materials; technology for producing natural products derived from plant, animal, and microbial sources; rapid prototyping and manufacture technology suitable for remote site and on-demand production processes; technology to promote the recovery, reuse, and remanufacture (recycling) of medical materials and equipment; technology for manufacturing biomedically specialized computational and information technology equipment and software; and development of innovative products that facilitate the safety and health training of hazardous materials workers, emergency responders, and skilled support personnel.

For more information, potential applicants should contact Dr. Thomas Miller, Program Director, Technology Development Group, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2139, Bethesda, MD 20892; telephone: 301-496-1779; fax: 301-402-1501; e-mail: mailto:tm208y@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://grants.nih.gov/grants/guide/pa-files/PA-04-161.html.

Research on Pathogenesis and Therapies for Muscular Dystrophy Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung, and Blood Institute (NHLBI) encourage grant applications for research on pathogenesis and therapies for the muscular dystrophies.*

Muscular dystrophies collectively have a high impact on health, affecting tens of thousands of people in the United States alone. These diseases are characterized by progressive weakness and wasting of muscles. Many cases of muscular dystrophy represent new occurrences of disease, where there is no prior family history. Research is needed to learn more about pathogenesis of the diseases and to improve early detection, diagnosis, treatment, and prevention.

Areas of potential research interest include, but are not limited to: understanding how protein deficiencies, triplet repeats, other chromosomal rearrangements, and molecular factors directly contribute to muscular dystrophy; identifying genetic and environmental factors that determine risk or modify disease onset, symptoms, progression, or outcome; developing and testing improved molecular diagnostics for all forms of muscular dystrophy; identifying disease-associated biomarkers and developing efficient newborn screening strategies; generating, breeding, and studying animal models for all of the muscular dystrophies, and utilizing these models in the development of potential therapeutic strategies; optimizing steroid treatment regimens based on patient characteristics to limit disease progression and minimize adverse side effects; and developing and testing new rehabilitative strategies to limit disease progression and prevent secondary complications.

For more information, potential applicants should contact Dr. John Porter, Program Director, Channels, Synapses and Circuits Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2142, Bethesda, MD 20892; telephone: 301-496-1917; fax: 301-402-1501; e-mail: jp477n@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PA-05-038.html.

Applications for Research Supplements to Promote Diversity in Health-Related Research Encouraged

The National Institute of Neurological Disorders and Stroke (NINDS) and all other institutes and centers of the National Institutes of Health (NIH) encourage grant applications for research supplements to promote diversity in health-related research.*

The NIH recognizes a unique and compelling need to promote diversity in the biomedical, behavioral, clinical, and social sciences research workforce. The NIH expects that efforts to diversify the workforce will lead to the recruitment of the most talented researchers from all groups; improve the quality of the educational and training environment; balance and broaden the perspective in setting research priorities; improve the ability to recruit subjects from diverse backgrounds into clinical research protocols; and improve the Nation's capacity to address and eliminate health disparities.

Candidates eligible for support under this supplement program include individuals at various career levels who come from groups that are underrepresented in science. Such candidates include individuals from underrepresented racial and ethnic groups, individuals with disabilities, and individuals from disadvantaged backgrounds. Detailed eligibility criteria are described in the full announcement.

For more information, potential applicants should contact Dr. David Jett, Program Director, Office of Minority Health and Research, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2149, Bethesda, MD 20892; telephone: 301-496-6035; fax: 301-594-5929; e-mail: dj140o@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://grants.nih.gov/grants/guide/pa-files/PA-05-015.html.

Research to Improve the Chemistry and Targeted Delivery of RNAi Molecules Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites small business innovation research (SBIR) and small business technology transfer (STTR) grant applications to develop new approaches and chemical modifications to increase the long-term stability, delivery, and targeting of siRNAs (short-interfering RNA) in cells and tissues for laboratory and therapeutic applications. This announcement is made together with 12 other components of the National Institutes of Health (NIH).*

RNA interference (RNAi) has emerged as a powerful strategy for silencing genes and has become a widely used tool due to its great simplicity and high efficiency. The possible therapeutic applications of RNAi are broad and far reaching, ranging from acquired diseases, such as viral infections, to genetic disorders, particularly where there is a dominant gain-in-function mutation. The discovery of RNAi has revolutionized genetic research, and is on the verge of spawning an entirely new class of drugs to treat human genetic diseases, provided that significant barriers in delivery and targeting can be overcome.

Research areas of interest include, but are not limited to, studies to develop: nucleic acid modifications leading to resistance to nuclease digestion but still allowing efficient processing by Dicer; chemical modifications that enhance base-pairing interactions between the siRNA and targeted mRNA; chemical modifications that will allow or regulate distribution to target tissues, such as to and across the blood-brain barrier; improved instrumentation that will synthesize long oligonucleotides reliably and with high fidelity; and systems for conditional expression of siRNAs. Also of interest are studies to: develop and identify chemical modifications to improve thermal stability of dsRNA, such as LNA (locked nucleic acids) or HNA (hexitol nucleic acids); identify chemical modifications leading to preferential strand uptake by RISC that will enhance specificity and reduce off-target effect; and identify chemical modifications, such as phosphorothioate linkages that will enhance the pharmacokinetic properties of siRNA.

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: 301-402-1501; e-mail: dt39y@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://grants.nih.gov/grants/guide/pa-files/PA-06-003.html.

Research on Restless Legs Syndrome and Periodic Limb Movement Disorder Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invite grant applications for research on restless legs syndrome (RLS) and periodic limb movement disorder (PLMD).*

RLS is a common neurological disorder characterized by unpleasant sensations of the legs and an urge to move them for relief. Because symptoms are intensified by inactivity and lying down, RLS patients often have difficulty falling asleep and staying asleep. Left untreated, RLS causes exhaustion and fatigue, which can affect occupational performance, social activities, and family life. An estimated 80 percent of RLS patients also have PLMD, which is characterized by repetitive stereotyped movements of the limbs, primarily the legs, during sleep.

Areas of research interest include, but are not limited to, studies of: the relationship between sensory gating and sleep as it may pertain to RLS; the inter-relationships among circadian rhythms, sleep, central nervous system dopamine levels, and RLS and PLMD; other oscillatory phenomena and possible relationship to PLMD and sensory symptoms in RLS; previously unexplored treatments for RLS and PLMD; and the relationship between opiate sensitivity and sensory symptoms. Also encouraged are studies to: identify biological markers that can be used in diagnostic or treatment studies; elucidate pathways linking RLS and PLMD to other sleep disorders, excessive daytime sleepiness, or metabolic or cardiovascular comorbidities associated with disturbed sleep; distinguish genetic and non-genetic forms and to map, identify, and characterize genes involved in the etiology of RLS-PLMD; develop genetic models of RLS and PLMD in both small and large animals; conduct studies in animals exposed to precipitants of RLS and PLMD; and compare periodic limb movements in RLS and other conditions.

For more information, potential applicants should contact Dr. Merrill Mitler, Program Director, Systems and Cognitive Neuroscience Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2108, Bethesda, MD 20892; telephone: 301-496-9964; fax: 301-402-2060; e-mail: mm777k@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PA-05-032.html.

Applications for Research on Rett Syndrome and MECP2 Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), the National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Association (IRSA), and the Rett Syndrome Research Foundation (RSRF) encourage grant applications for research on Rett syndrome (RTT) and the MECP2 gene.*

RTT is a severely debilitating neurodevelopmental disorder for which there is no cure; current treatment is symptomatic only. Until recently, little progress had been made in understanding the cause of RTT or in developing approaches for its treatment. However, the demonstration that mutations in the MECP2 gene are responsible for the majority of cases of RTT suggests new avenues for research and therapy development.

Areas of research interest include, but are not limited to: developmental, neuroanatomical, osteological, electrophysiological, and imaging studies to identify specific abnormalities in RTT patients or in animal models of RTT; studies of transcriptional and post-transcriptional regulation of MECP2 expression in neurodevelopment and neuronal maturation; identification of genomic targets of MECP2 actions; identification and analysis of gene mutations (or polymorphisms) in RTT patients or RTT animal models, including genotype-phenotype investigations of RTT; investigation of the role of MECP2 in other neurological or neurobehavioral disorders, and studies of other conditions and clinical abnormalities that co-occur in families of individuals with RTT; development of more sophisticated cellular or animal models for RTT; neurodevelopmental and longitudinal studies of RTT patients that investigate the neuropathological progression and inherent variability of the disease; identification of the downstream molecular targets of MECP2 with a focus on potential molecular targets for drug therapy of RTT; clinical studies of the problems that afflict children and adults with RTT; and clinical studies including genotype-phenotype analyses that will provide a rational foundation for the treatment or management of RTT.

For more information, potential applicants should contact Dr. Laura Mamounas, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2132, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-402-1501; e-mail: lm92t@nih.gov.

*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PAS-05-024.html.

Applications for Identifying Autism Susceptibility Genes Requested

The National Institute of Neurological Disorders and Stroke (NINDS) requests applications for research to identify autism susceptibility genes. This announcement is made together with 4 other components of the National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR), the Health Research Board, Ireland (HRB), the Southwest Autism Research and Resource Center (SARRC), Cure Autism Now (CAN), and the National Alliance for Autism Research (NAAR).*

Autism is a complex neurodevelopmental disorder with early childhood onset. A variety of research designs have been applied to enhance our understanding of the genetic basis of the disorder. However, autism's mode of inheritance is complex and no simple genetic model seems to fit its familial transmission. The purpose of this request for applications (RFA) is to support state-of-the-art research to identify specific genes and gene variants in localized chromosomal regions that present susceptibility to autism.

Areas of research interest include, but are not limited to: studies to identify specific genetic variants that influence risk to autism and lie within pre-existing candidate linkage regions; prioritizing candidate genes and the application of high-throughput approaches for characterization of single nucleotide polymorphisms (SNPs); sequencing and resequencing candidate genomic regions and/or construction of comprehensive, high-density SNP linkage disequilibrium maps, when such resources are used in conjunction with tests of candidate SNPs and haplotypes for their association with autism; analysis of methylation patterns in CpG dinucleotides located in regulatory regions of genes where there appear to be epigenetic effects on gene expression in autism; identification and analysis in families of paternally/maternally expressed genes that are likely candidates for autism susceptibility genes; and in vitro and mouse (or other animal) studies that specifically explore the functional contribution of any susceptibility gene(s) identified by fine mapping activities in humans.
LETTERS OF INTENT RECEIPT DATE: March 19, 2005.
APPLICATION RECEIPT DATE: April 19, 2005.

For more information, potential applicants should contact Dr. Laura Mamounas, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2132, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-402-1501; e-mail: lm92t@nih.gov.

* For a full list of supporting NIH components and a more detailed description of this request for applications, please visit the NIH web site at: http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-05-007.html.

NINDS Seeks Children and Adults with Cerebral Palsy

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) seek children and adults with cerebral palsy (CP) for research studies. These studies (protocols #04-N-0098, #01-N-0260, and #05-N-0066) include a comprehensive rehabilitation assessment, functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS) of the brain, motor learning studies, and muscle reflex studies. The investigators plan to examine brain function in children and adults with CP and to examine how constraint-induced therapy affects brain function in a subset of children with hemiplegic CP. The duration of the studies will vary from a 2-day outpatient evaluation to a 3-week outpatient treatment study. Eligible participants must be 6 to 30 years of age and have either diplegic (affects the legs more than the arms) or hemiplegic (affects only one side of the body) CP.

Persons whose CP developed after 1 year of age are not eligible to take part in these studies. In addition, persons who have metal implants in their body, a severe seizure disorder, sickle cell disease, cardiac disease, another serious medical disorder, or had surgery to treat muscle stiffness in their arm or hand are not eligible. Pregnant women are not eligible to participate.

The studies will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. Compensation is provided to all participants. There is no cost for participation or for any tests associated with the research. Patients who are eligible for the treatment study may have to pay for their therapy. For more information, with no obligation to participate, please contact the NIH Patient Recruitment and Public Liaison Office at 1-800-411-1222 (TTY: 1 866-411-1010). Refer to study numbers #01-N-0260, #04-N-0098, or #05-N-0066.

NINDS Seeks Persons with Parkinson’s Disease

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) seek persons with Parkinson's disease for a research study. In the study, investigators plan to use a device to see if stimulation of certain areas of the brain, along with the patient's current medications, will improve movement, balance, and walking. The study will last approximately 4 weeks and include eight stimulation sessions. Each session will last approximately 1 hour.

Eligible participants must be 40 to 80 years of age and be taking an L-DOPA medication such as Sinemet. Persons who have metal implants in their body, other significant medical or psychiatric illness, or a history of seizures are not eligible.

The studies will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. Compensation is provided to all participants. There is no cost for participation or for any tests associated with the research. 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.

For more information on protocol #03-N-0116, with no obligation to participate, please contact Dr. Mikhail Lomarev, NINDS, NIH, Building 10, Room 5N240, 10 Center Drive MSC 1428, Bethesda, MD 20892-1428; telephone: 301-594-0937 or 301-435-8518; fax: 301-480-2286; e-mail: LomarevM@ninds.nih.gov.