Funding News - NINDS Notes - June 2003

Applications for Development of PET and SPECT Ligands for Brain Imaging Studies Sought

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), the National Institute of Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and the National Institute on Drug Abuse (NIDA) request research grant applications for the development of novel radioligands for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging in the brain.*

Tremendous opportunities exist for using PET and SPECT imaging in studies of the pathophysiology and treatment of brain disorders, but relatively few radioligands are currently available for functional imaging of target molecules implicated in normal brain function, aging, and brain and behavioral disorders.

Potential areas of research interest include: lead compound identification/development and syntheses of chemicals with suitable binding affinity, biodistribution, pharmacokinetics, and physio-chemical properties allowing radiochemical synthesis; pre-clinical studies to screen out compounds that are unlikely to be promising candidates for PET or SPECT imaging; radiolabeling procedures; in vitro and ex vivo autoradiography; in vivo imaging including micro PET (rodent and/or primate); studies of pharmacological specificity, biodistribution, and pharmacokinetics; model development for quantitation, including development and evaluation of pharmacokinetic models and use of animal models of gradient of binding sites/enzymes to assess sensitivity to changes; determination of toxicology/pathology (FDA approved) for submission of a Radioactive Drug Research Committee (RDRC) or Investigational New Drug (IND) application; IND application development and submission to the FDA prior to pilot human studies; pilot human imaging studies with normal controls, pharmacological challenges with analyses of radiometabolites under the auspices of IRB approval (i.e., RDRC or IND development and submission); and clinical studies in patient/disease populations or experimental manipulations.

For more information, potential applicants should contact Dr. Emmeline Edwards, Program Director, Systems and Cognitive Neuroscience Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2109, Bethesda, MD 20892; telephone: 301-496-9964; fax: 301-402-2060; e-mail: ee48r@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-03-112.html.

Emerging Technologies to Study Reproductive Neuroendocrinology Sought

The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Child Health and Human Development (NICHD) encourage grant applications for emerging technologies to study nervous system control of reproduction.*

The purpose of this program announcement is to stimulate the development of new technologies and the application of existing innovative technologies to answer questions regarding the neuroendocrine control of reproduction that previously could not be answered due to limitations in technology.

The NINDS is particularly interested in the application of innovative technologies to study neural control of reproductive function in clinical populations and animal models of neurological disorders where reproductive function is compromised. Other areas of research interest include: non-invasive, high-resolution brain imaging techniques to assess in vivo changes in hypothalamic reproductive function; electrophysiological, cell imaging, and molecular techniques for the in situ assessment of the activity of gonadotropin-releasing hormone (GnRH), and of other neurons involved in the control of GnRH neuronal function; laser capture microdissection approaches coupled to gene profiling technology to define the existence of cell-specific changes in gene expression in phenotypically identified cells within the neuroendocrine brain and pituitary gland; genomic and genetic approaches to identify novel genes and gene networks involved in the neuroendocrine control of reproduction; and nanotechnology to identify the sub-cellular mechanisms underlying the transsynaptic and glial control of GnRH neuronal function.

For more information, potential applicants should contact Dr. Emmeline Edwards, Program Director, Systems and Cognitive Neuroscience Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2109, Bethesda, MD 20892; telephone: 301-496-9964; fax: 301-402-2060; e-mail: ee48r@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-03-079.html.

Applications for Research on Glial Cell Inflammatory Mechanisms of HIV-1 Induced Cell Injury in the Nervous System Sought

The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) encourage applications for research on the role of neuroinflammation in the initiation and expansion of cellular injury and death in HIV-1 infection of the central nervous system (CNS).*

Neurological dysfunction is a devastating complication of HIV-1 infection. Recent evidence indicates that microglial and astrocytic activation results in the release of excitotoxins, arachidonic acid metabolites, reactive oxygen species, cytokines, and chemokines that lead to neurodegeneration and cognitive impairment in HIV-1 infected individuals. The pathophysiological mechanisms underlying the changes in neurological function are as yet unresolved but may include neuroinflammatory responses to HIV-1 infection.

Examples of potential areas of research interest include studies to: investigate the role of microglia and astrocytes in the etiology of AIDS dementia; advance studies on cell-cell interactions in the neuroinflammatory cascade; investigate the roles of excitotoxicity, the production of nitric oxide, and the production of reactive oxygen species as mechanisms of neuropathogenesis in HIV-1 infection of the CNS; define phenotypic markers which characterize activated microglia and astrocytes in the context of HIV-1 infection of the nervous system; delineate the contribution of microglia and astrocytes to the development of inflammation of the HIV-1 infected CNS via antigen presentation or production of specific cytokines and chemokines; investigate contributions of perivascular microglia and astrocytes to the entry of blood macrophages into the CNS across the blood-brain barrier; investigate the role of HIV-1 proteins in the activation of microglia and astrocytes, or their role in mediating damage to neurons; develop animal models of HIV-1 induced neuroinflammation; develop assays that use human neurons as targets of HIV-1 induced neuroinflammation; and delineate apoptotic pathways involved in the death of CNS cells in the context of HIV-1 infection.

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/PAS-03-084.html.

Applications for Innovations in Biomedical Computational Science and Technology Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites grant applications for innovative research in biomedical computational science and technology to promote the progress of biomedical research. This announcement is made together with 16 other components of the National Institutes of Health (NIH), and is also being offered to the small business community.*

Computing and computational tools have become increasingly important in enabling progress in biomedical research. The promotion of the interface of biomedical information science and technology with biomedical research should result in new digital and electronic tools that will have substantial impact on broad areas of biomedical research. Biomedical computing or biomedical information science and technology includes database design, graphical interfaces, querying approaches, data retrieval, data visualization and manipulation, data integration through the development of integrated analytical tools, and tools for electronic collaboration, as well as computational and mathematical research including the development of structural, functional, integrative, and analytical models and simulations.

Examples of potential areas of research interest include: tools for data acquisition, archiving, querying, retrieval, visualization, integration, and management; platform-independent translational tools for data exchange and for promoting interoperability; analytical and statistical tools for interpretation of large data sets; and new models or simulations of complex biological processes (and the development of mathematical tools for these processes).

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://grants.nih.gov/grants/guide/pa-files/PAR-03-106.html. For a detailed description of the small business (SBIR/STTR) program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PAR-03-119.html.

Research on the Neurobiology of Complex Regional Pain Syndrome/Reflex Sympathetic Dystrophy Sought

The National Institute of Neurological Disorders and Stroke (NINDS) invites grant applications for research on the neurobiology of complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy (RSD).*

CRPS/RSD is a chronic debilitating condition characterized by severe burning pain, pathological changes in bone and skin, excessive sweating, tissue swelling, and extreme sensitivity to touch. Though highly debated, the syndrome is thought to evolve through three stages-acute, dystrophic, and atrophic-each marked by progressive pain and physical changes in the skin, muscles, joints, and bones. The cause of CRPS/RSD is unknown, and most treatments for symptoms of the disorder are not optimal.

Areas of potential research interest may include: development and validation of animal models that replicate the unique features of CRPS/RSD; characterization of neurobiological mechanisms of CRPS/RSD including peripheral afferent and efferent mechanisms, central mechanisms, and factors that influence these processes; studies of neurotransmitter systems and neuropeptides involved in CRPS/RSD; studies of signaling mechanisms in CRPS/RSD; research on the immune system mechanisms and autoimmune inflammatory processes in CRPS/RSD; studies of the role of estrogen (genomic and non-genomic effects) in the pathophysiology of CRPS/RSD; translational studies that integrate the research paradigms validated in animal and human models with clinical research on patients; studies of gene and protein expression profiling in models of CRPS/RSD; development of new CRPS/RSD therapies for prospective clinical trials; development of standardized diagnostic criteria for CRPS/RSD; assessment of risk factors and incidence of CRPS/RSD through epidemiological studies; studies of disease mechanisms that give rise to CRPS/RSD in susceptible individuals; and studies that assess the effect of gender, age, and co-morbid neurological conditions on the development and maintenance of CRPS/RSD.

For more information, potential applicants should contact Dr. Emmeline Edwards, Program Director, Systems and Cognitive Neuroscience Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2109, Bethesda, MD 20892; telephone: 301-496-9964; fax: 301-402-2060; e-mail: ee48r@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-03-120.html.

Applications for Research on Rett Syndrome and MeCP2 Encouraged

The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Child Health and Human Development (NICHD) encourage grant applications for basic and clinical research on Rett syndrome and MeCP2.*

Rett syndrome is a severely disabling childhood neurological disorder that affects 1 in 10,000-15,000 females. Until recently, little progress had been made in understanding the cause of the disorder or in developing approaches for treating it. However, the demonstration that mutations in the MeCP2 gene cause Rett suggests new avenues for research and therapy development.

Examples of potential areas of research interest include: developmental, neuroanatomical, electrophysiological, and imaging studies intended to identify specific abnormalities in Rett patients or in animal models of Rett; studies of the role of the MeCP2 gene product in basic cellular processes; structure/function analyses of MeCP2; investigation of the role of MeCP2 in other neurological or neurobehavioral disorders, and studies of other conditions and clinical abnormalities that co-occur in the families of individuals with Rett; identification and analysis of genes misexpressed in Rett patients or Rett animal models; development of more sophisticated animal models for Rett; neurodevelopmental and longitudinal studies of Rett patients that investigate the neuropathological progression and inherent variability of the disease; identification of potential molecular targets for drug therapy of Rett; pre-clinical screening of potential therapeutic agents in cellular or animal models of Rett; clinical studies of the problems that afflict children with Rett, including autonomic disorders and difficulties with literacy and communication; and clinical trials of therapeutic agents for the treatment or management of Rett.

For more information, potential applicants should contact Dr. Robert Finkelstein, Program Director, Neurogenetics Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2143, Bethesda, MD 20892; telephone: 301-496-5745; fax: 301-402-1501; e-mail: rf45c@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-03-097.html.

Patients with Cervical or Focal Hand Dystonia Sought

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) seek people with cervical or focal hand dystonia who are receiving botulinum toxin injections for a study of a medication called amlodipine. This research study will examine whether amlodipine can improve the effect of botulinum toxin injections for dystonia, which causes abnormal postures and disrupted movements.

The study 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.

For more information, physicians should contact Dr. Barbara Karp, Office of the Clinical Director, NINDS, NIH, Building 10, Room 5S209, 10 Center Drive MSC 1428, Bethesda, MD 20892-1428; telephone: 301-496-0150; fax: 301-480-2973. Please refer to study number 01-N-147.

Patients with Syringomyelia Sought for Study

Investigators at the National Institute of Neurological Disorders and Stroke (NINDS) seek patients with syringomyelia for a study of the cause of the disorder, which may be due to a blockage of spinal fluid or from a spinal cord tumor.

This study will take place at the National Institutes of Health (NIH) Clinical Center, Bethesda, MD. Patients will undergo testing both before and after receiving surgical treatment for this condition. The testing and surgical treatment will be provided at the NIH, and all treatment-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 be eligible, patients must be 18 to 70 years old and must have a syrinx (fluid-filled cavity in the spinal cord). Patients who are pregnant, breastfeeding, or suffering from bleeding disorders will not be accepted.

For more information, physicians should contact Dr. Edward H. Oldfield, Chief, Surgical Neurology Branch, NINDS, NIH, Building 10, Room 5D37, 10 Center Drive MSC 1414, Bethesda, MD 20892-1414; telephone: 301-496-5728. Refer to study number 01-N-0085.

NINDS Seeks Persons with Tourette Syndrome

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) seek persons with Tourette syndrome (TS) for neuroimaging research studies. These studies include functional magnetic resonance imaging (fMRI) [Protocols 02-N-0027], positron emission tomography (PET) [Protocols 02-N-0175 and 02-N-0181], and magnetic resonance spectroscopy (MRS) [Protocol 02-N-0128].

Eligible individuals must be 14 to 65 years old. Participants will be asked to stop any medications that affect the central nervous system and to abstain from alcohol for 24 hours before the study. Persons with progressive neurological disorders, other than TS, or other significant pathology will be excluded. Pregnant women will be excluded.

The purpose of the studies is to examine brain activity of tics during waking (fMRI and PET) and sleeping (PET) states. Furthermore, the studies will evaluate the density of GABA A receptors (PET) and look at brain metabolism of GABA (MRS). Researchers hope to reveal which brain areas generate tics and how the neurotransmitter GABA is involved.

Individuals may participate in one or more of the above studies if they qualify. The studies may last two to three hours as part of an outpatient visit or may last up to two days and require hospitalization. Once the studies are complete, individuals will be given information on the results.

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

For more information, with no obligation to participate, please contact Dr. Stephan Bohlhalter at 301-496-0153, fax 301-480-2286, e-mail: BohlhalS@ninds.nih.gov; Dr. Alicja Lerner at 301-402-2983, fax 301-480-2286, e-mail: LernerA@ninds.nih.gov; or Dr. Fernando Pagan at 301-402-3494, fax 301-480-2286, e-mail: PaganF@ninds.nih.gov.