TwitterRSSFacebookDirectors Blog
  Disorders A - Z:   A    B   C    D    E    F    G    H    I    J    K    L    M    N    O    P    Q    R    S    T    U    V    W    X    Y    Z

Skip secondary menu

Selected NINDS ARRA Grants

Title Institute & Investigator Overview Key Topic Areas
Molecular Determinants of Axonal RNA Translation Alfred I. Du Pont Hospital for Children: Jeffery L. Twiss

The researchers will investigate key mechanisms involved in the regeneration of injured nerves.

This project aims to dissect the mechanisms involved in axonal RNA transport and local protein synthesis during regeneration of injured nerves.
Neuropathy; Regenerative Medicine
Nonrecurrent Rearrangements, Genome Architecture and Neurodegenerative Disease Baylor College of Medicine: James Lupski

The investigators will explore how genetic changes cause Charcot-Marie-Tooth disease and other neurodegenerative disorders.

This project addresses the mechanisms by which novel genetic rearrangements cause a variety of neurological disorders, including Alzheimer's, Parkinson's, and Charcot-Marie-Tooth.
Charcot-Marie-Tooth Disease; Clinical Research; Genetics; Human Genome; Neurodegeneration
Static and Dynamic Organization of Primate Motor Cortex Brown University: John P. Donoghue

This work explores the fundamental circuits and neural processing that control arm, wrist and hand actions; discoveries in this area could lead to improved neural prosthesis systems for robotic arms to aid people with severe paralysis.

These studies will reveal fundamental principles of cortical information processing that underlie the generation of flexible arm, wrist, and hand actions. In addition, these results will determine the potential to generate a multidimensional control signal that could potentially be used by neural prosthesis systems to recreate flexible reach and grasp actions of robotic arms or paralyzed muscles for persons with severe paralysis.
Neural processing; Neural prosthetics
Evaluation of Wire Electrodes to Activate the Expiratory Muscles to Restore Cough Case Western Reserve University: Anthony F. DiMarco

The investigator will evaluate a minimally invasive method of electrical activation of muscles to help people with spinal cord injury.

Due to their inability to cough, respiratory complications such as pneumonia are a major cause of disability and death in subjects with spinal cord injury. The purpose of the proposed study is to evaluate a minimally invasive method of electrical activation of the expiratory muscles to restore cough utilizing spinal cord wire electrodes which can be inserted percutaneously. This technique would likely have wide patient and physician acceptance, significantly reduce the need for caregiver support, facilitate management of respiratory secretions, reduce the incidence of respiratory tract infections, reduce costs and improve life quality.
Spinal Cord Injury; Clinical Research; Trauma (Head and Spine); Lung; Neurodegeneration; Rehabilitation
Attenuating the Retinal and CNS Adverse Effects of Vigabatrin with NKCC1 Inhibitors Children's Hospital Boston: Frances E. Jensen

This research seeks to improve the safety of vigabatrin, an anti-epileptic drug.

Epilepsy affects over one percent of the U.S. population, and up to 30 percent of people suffering from epilepsy do not respond to conventional antiepileptic drugs (AEDs). The newly FDA-approved AED vigabatrin has improved efficacy in this population yet its use has been limited by a 30% incidence of severe irreversible retinal and brain toxicity. The present proposal addresses mechanism of toxicity and proposes to attenuate this with a novel agent bumetanide, which has a good safety profile in humans in its use for unrelated indications. No current treatment for the irreversible side effects of vigabatrin exists, and successful demonstration of efficacy of bumetanide in animal models of vigabatrin toxicity proposed here will facilitate clinical trials in patients receiving vigabatrin for refractory epilepsy.
Epilepsy; Eye Disease and Disorders of Vision; Neurodegeneration; Pediatric Studies; Prevention
Inhibition Separating Touch and Pain Columbia University Health Sciences: Amy B. MacDermott

This work focuses on the neuronal circuitry and molecules within the spinal cord that allow some forms of chronic pain to develop in order to identify potential therapies.

Chronic pain is an important and debilitating medical problem for many people within the United States and worldwide. This proposal is directly focused on identifying the neuronal circuitry and molecules within the spinal cord that allow some forms of chronic pain to develop. Improved understanding of this circuitry and associated receptors and molecules will greatly improve the rate of drug discovery to help control chronic pain.
Pain (Chronic); Neuropathy
Identification of Compounds to Treat Charcot-Marie-Tooth type 2E Neuropathy Columbia University Health Sciences: Ronald K. Liem

This work develops chemical screening to identify novel drugs to treat a type of Charcot-Marie-Tooth disease and test them in mouse models of the disorder.

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited form of peripheral neuropathy. The goal of this project is to use chemical screening to identify novel drugs to treat one type of CMT and test them in mouse models of the disease.
Charcot-Marie-Tooth Disease; Genetics; Neurodegeneration; Neuropathy; Orphan Drug; Pain (Chronic)
Ectopic Granule Cells in Epilepsy Duke University: J. Victor Nadler

The investigator is examining granule cells -- small neurons -- whose growth and formation are affected by seizures in epilepsy.

Many of the new dentate granule cells produced as a result of seizures migrate aberrantly into the hilus of the hippocampus and provide a source of excitation that can lead to epilepsy. Understanding these aberrant neurons may suggest therapeutic strategies to eliminate this source of excitation.
Epilepsy; Neurodegeneration
Mechanisms of Limbic Epileptogenesis Duke University: James O. McNamara

Building on previous research linking the onset and progression of epilepsy with specific brain receptors, researchers will develop an animal model to focus understanding of the mechanisms of disease and to develop novel therapies.

Understanding the mechanisms of limbic epileptogenesis may lead to novel disease modifying therapies. Epileptogenesis is associated with enhanced activation of TrkB in the mossy fiber pathway of hippocampus. The neurotrophin receptor, TrkB, is required for epileptogenesis in the kindling model. The investigators seek to determine whether inhibiting TrkB signaling prevents other types of epileptogenesis in animal models. This information will guide efforts aimed at exploiting TrkB as a molecular target for anti-epileptogenic therapies.
Epilepsy; Neurodegeneration; Prevention
Dopamine, Mutant Synuclein, Oxidative Stress and Inflammation Georgetown University: Howard J. Federoff

This project will focus on inflammation causing molecules and immune cells in the brain and spinal cord and their role in the onset and progression of Parkinson's disease.

This project will examine the role of pro-inflammatory molecules and microglia during the initiation and progression of Parkinson's disease in order to identify potential therapies.
Parkinson's Disease; Genetics; Neurodegeneration;
Bioengineered Scaffolds for Peripheral Nerve Repair Georgia Institute of Technology: Ravi V. Bellamkonda

The goal of this project is to find new ways to regenerate peripheral nerves injured by trauma or surgery.

Peripheral nerve defects from trauma or tumor resection result in significantly decreased quality of life. Goal of the proposed work is to significantly enhance peripheral nerve regeneration.
Neuropathy; Neurodegeneration; Regenerative Medicine; Transplantation; Nanotechnology
Sphingosine 1-Phosphate Receptors and Sensitization of Sensory Neurons Indiana University-Purdue University at Indianapolis: Grant D. Nicol

This study focuses on interactions between the immune system and the nervous system that lead to chronic pain following inflammation.

This proposal will address the interactions between the immune system and the nervous system that lead to chronic pain following an inflammatory response to injury or disease. It will help to identify interventions to reduce chronic inflammatory pain.
Pain (Chronic); Genetics; Neuroinflammation
DTIStudio: Resource Software for Diffusion Tensor Imaging Johns Hopkins University: Susumu Mori

Neuroimaging is critical in diagnosing brain white matter injuries. The software developed under this grant will aid clinicians in diagnosing and treating neurological disorders.

Diffusion tensor imaging (DTI) is critical in diagnosing brain white matter injuries. The software developed under this grant will aid clinicians to diagnose and treat neurological disorders.
Neuroimaging; Diagnostic Radiology
ALS Therapies and Genomics for Mutant TDP-43 and TLS/FUS Ludwig Institute for Cancer Research: Don W. Cleveland

Scientists will develop animal models of ALS and use very high throughput genetic sequencing to identify genes and potential new approaches for therapy.

A paradigm shift in understanding what goes wrong in the fatal motor neuron disease Amyotrophic Lateral Sclerosis has been initiated by the discoveries that mutations in a pair of RNA binding proteins (TDP-43 and FUS/TLS) are primary causes of the disease. Through construction and analysis of mice that are genetic mimics of inherited ALS, how these mutations cause premature death of motor neurons will be identified. New, very high throughput DNA/RNA sequencing methods will be used to identify genes whose expression is altered by the mutations, thereby identifying new targets and approaches for devising a successful therapy for ALS.
Amyotrophic Lateral Sclerosis (ALS); Genetics; Human Genome; Neurodegeneration; Biotechnology
Genetics of Microangiopathic Brain Injury Mayo Clinic College of Medicine: Stephen T. Turner

This project will use a genomic strategies to identify genetic variants that may contribute to structural brain injury.

Although genetic susceptibility is known to contribute to risk of stroke and dementia, most of the genes and the mechanisms by which injury to brain structure and function occurs remain unknown. Since genetically determined alterations in gene expression are likely to be a major mechanism accounting for statistical associations between genetic polymorph isms and variation in susceptibility to brain injury, this project will utilize a functional genomic strategy, based on gene expression profiles measured in human lymphocytes, to identify genetic variants that alter gene expression levels and thereby contribute to inter-individual differences in magnetic resonance imaging measures of structural brain injury. Such identification of genetic variants with functional effects contributing to alterations in structural brain injury may lead to improved methods of detection, evaluation, treatment, and prevention of stroke and dementia.
Stroke; Aging; Biotechnology; Clinical Research; Diagnostic Radiology; Genetics; Human Genome
Huntington's Disease and the Striatum Mount Sinai School of Medicine of NYU: Michelle E. Ehrlich

This study will explore gene expression in brain cells in pursuit of potential therapeutic targets for Huntington's disease.

Huntington's disease is a fatal neurodegenerative disease which despite ubiquitous protein and mutation expression, selectively affects the medium size spiny neurons of the striatum. Using novel molecular approaches, the investigators will explore the mechanism of cell specificity in order to determine whether/and how, therapy may be directly targeted to the at-risk neuronal population. Knowledge of gene expression in striatum, will also be relevant to other diseases, e.g. addiction, dystonia, and Parkinson's.
Huntington's Disease; Neurodegeneration; Aging
Presynaptic NMDA Receptors in the CNS Oregon Health and Science University: Craig E. Jahr

This project investigates synaptic activity that affects learning and memory and neuronal death.

This project investigates NMDA synaptic localization and the modulation of neurotransmitter release, which affects plasticity in learning and memory and neuronal death in ischemia and neurological diseases.
Brain Plasticity; Learning and Memory; Neuronal Death
Development of an Instrumented System to Measure Mobility in Parkinson's Disease Oregon Health and Science University: Fay Bahling Horak

New technology will be tested to monitor problems with balance and gait associated with Parkinson's disease.

This project will use new technology to develop objective instruments and centralized monitoring of balance and gait for Parkinson's disease and other neurological disorders. These new tools will permit clinical trials aimed at reducing mobility disability to be completed with fewer subjects, shorter duration, and less cost.
Parkinson's Disease; Aging; Bioengineering; Clinical Research; Clinical Trials; Neurodegeneration; Prevention
Migraine Headache and Central Pain Facilitating Systems Oregon Health and Science University: Mary M. Heinricher

This study will explore processes in the central nervous system (CNS) linked with migraine.

Millions of people suffer from migraines, yet scientists know little about the mechanisms by which they are generated. This proposal will explore processes in the central nervous that are linked to the pathophysiology of migraine pain.
Migraine; Pain (Chronic)
MicroRNA Networks in Synaptic Plasticity Oregon Health and Science University: Richard H. Goodman

This project explores a novel method to pinpoint microRNAs (small strands of genetic material with powerful abilities to control gene expression) and explore their impact on neuronal activity in neurological and psychiatric disease.

This project describes a novel method for determining which microRNAs bind to the 3'UTR sequences of p250GAP and LimKI, two proteins that have been proposed to regulate the formation of synaptic spines in response to growth factors and neuronal activity. This method is critical for understanding the contribution of microRNA pathways to neurological and psychiatric disease. MicroRNAs are believed to contribute to schizophrenia, autism, Tourette's syndrome, mood disorders, and fragile X syndrome.
Autism; Fragile X Syndrome; Schizophrenia, Tourette's Syndrome, Genetics; Mental Retardation
Virtual Realty Systems for Neural Circuit Dynamics Princeton University: David W. Tank

This study focuses on brain activity in animal models navigating a virtual reality environment; the results could lead to virtual reality systems that can compare normal and disease states in the brain.

This study will develop virtual reality systems for use in neuroscience research. The system will enable the measure of electrical and chemical processes in one or many individual neurons in the brain while the subject is navigating in a virtual environment. This capability would be valuable in comparing normal and diseased states in the brain. The methods developed will be applicable to the mouse, which is the leading mammalian genetic model in health research. It will also be developed for the rat, a species widely used in behavioral studies.
Neural circuits; Bioengineering
Viral Brainbow: Tracing Brain Circuits with Connection Order Specificity Princeton University: Lynn W. Enquist

Viral tracing involves using specially altered viruses to map neural circuits, providing a better understanding of nervous system functions.

Viral tracing of neural circuitry has become an essential tool in the neuroscience community. The new, robust viral tracers that will result from this work have promise to reveal detailed functional insights into trans-neuronal spread of herpesviruses, as well as neural circuit organization that have not been possible to achieve in the past. These neural tracers would be powerful tools to elucidate brain micro-circuitry, providing a better understanding of nervous system functions.
Brain Mapping; Neural Circuits; Bioengineering; Infectious Diseases
Neuron Target Interaction - a Developmental Genetic Study Rutgers State University: Karl Herrup

The researchers will explore new strategies to prevent neuronal cell loss, a problem in many diseases of the central nervous system (CNS).

These studies will explore new approaches to the prevention of the neuronal cell loss that occurs in multiple CNS diseases.
Neurodegeneration; Aging; Alzheimer's Disease; Biotechnology; Genetics
GM1 at the ER-mitochondrion Microdomains Regulates Ca2+ Signaling and Apoptosis St. Jude Children's Research Hospital: Alessandra D'Azzo

This work seeks to identify novel mechanisms of pathogenesis and may reveal basic biological processes controlled by GM1-gangliosidosis, a neurodegenerative disease in children.

GM1-gangliosidosis is a catastrophic neurodegenerative disease that affects infants and children for which there is no treatment. The investigators are in the position to gain full understanding of the events in this disease that cause cell death in the brain. The researchers are confident that these studies will enable the identification of novel mechanisms of pathogenesis and may reveal basic biological processes controlled by GM1. This knowledge is essential for designing new therapies for children with GM1-gangliosidosis and possibly those with other GSL storage diseases.
GM1-gangliosidosis; Lipid Storage Diseases; Pediatric Studies
Diffusion Weighted Imaging Evaluation For Understanding Stroke Evolution2: DEFUSE Stanford University: Gregory W. Albers

This study investigates how neuroimaging can identify patients who could benefit from clot-busting therapies several hours after stroke onset.

The key objective of DEFUSE 2 is to obtain the data required to optimally design a definitive study to assess the risks and benefits of treatment of selected stroke patients beyond the time window when the only currently proven effective therapy is available. The DEFUSE 2 study will clarify that specific MRI findings can identify a large subgroup of patients who benefit from therapies that restore blood flow to the brain many hours after symptom onset. These findings will eventually lead to effective therapies for a large population of stroke patients who are currently ineligible for treatment and substantially reduce stroke-related disability.
Stroke; Clinical Research; Clinical Trials; Diagnostic Radiology
Amino Acid Transport and the Biology of Human Gliomas University of Alabama at Birmingham: Harald W. Sontheimer

This work supports preclinical studies testing whether a clinically approved drug for Crohn's disease might also be used to treat malignant gliomas, lethal brain tumors.

This proposal seeks to provide a rationale to treat patients with malignant glial-derived brain tumors (glioma) and peritumoral seizures with the FDA approved drug Sulfasalazine, a clinically approved drug for the treatment of inflammatory bowl disorder (Crohn's).
Brain Cancer; Epilepsy; Neurodegeneration
NA/Bicarbonate Cotransporters in Brain University of Alabama at Birmingham: Mark Oliver Bevensee

This study looks more closely at biochemical processes associated with stroke and other neurological problems.

A better molecular understanding of the function of HCO3- transporters will be necessary in future protein-modeling studies. Because changes in ATP levels alter PIP2 levels, this project will contribute to an understanding of pH and associated ion dysregulation in energy-deficient pathologies such as anoxia/hypoxia, ischemia, stroke, and reperfusion injury.
Anoxia/Hypoxia, Ischemia, Stroke, Reperfusion Injury
Novel, Subtype Selective Potentiators of Nicotinic Acetycholine Receptors University of Alaska Fairbanks: Marvin K. Schulte

This study focuses on developing potential new drugs for Alzheimer's disease, autism, schizophrenia and other central nervous system (CNS) .

The study develops a natural product into a new class of drugs aimed at CNS disorders such as Alzheimer's disease, autism and schizophrenia.
Autism; Alzheimer's Disease; Aging; Mental Retardation; Neurodegeneration; Schizophrenia
Canonical Transient Receptor Potential Channels and Excitotoxicity University of Arkansas Medical Sciences Little Rock: Fang Zheng

By studying factors that trigger the death of neurons, scientists hope to identify ideas to develop treatments for epilepsy, stroke and other neurological diseases.

The neuronal cell death caused by over exposure to a neurotransmitter called glutamate is a shared event in several neurological diseases, such as epilepsy, stroke and head trauma. New and effective treatment options for these neurological diseases are needed. Detailed knowledge on the mechanism of glutamate-induced neuronal cell death will help to identify new molecular target for drug development. A set of newly discovered ion channels called the canonical transient receptor potential (TRPC) channels may contribute to glutamate induced cell death because they can be activated by a glutamate receptor called metabotropic glutamate receptors. By using both in vitro and in vivo models of epilepsy, this study will determine whether these TRPC channels contribute to the generation of seizure and seizure-induced neuronal cell death. Results from this study will aid future drug development that will provide new treatment options for many neurological diseases.
Brain Disorders; Epilepsy; Neurodegeneration; Neurosciences
A Mitochondrial Etiology of Autism University of California Irvine: Douglas C. Wallace

To determine if a subset of autism spectrum disease is caused by mitochondrial dysfunction, scientists will survey patient cell lines for mutations that alter mitochondrial genes; if mitochondrial defects are found, selected patients will be tested using non-invasive biophysical and biochemical tools to determine if they manifest a functional mitochondrial defect.

To determine if a subset of autism spectrum (ASD) disease is caused by mitochondrial dysfunction, the investigators propose to survey patient lymphoblastoid cell lines for those harboring nuclear DNA (nDNA) copy number variants (CNVs) or mitochondrial DNA (mtDNA) mutations that alter mitochondrial genes. Cell lines from the mutant patients will be tested for the expected mitochondrial function. If mitochondrial defects are found, selected patients will be tested using non-invasive biophysical and biochemical tools to determine if they manifest a functional mitochondrial defect.
Autism; Clinical Research; Genetics; Human Genome; Mental Retardation; Pediatric Studies
Genetics of Familial Episodic Ataxia University of California Los Angeles: Joanna C. Jen

The goal for the designated episodic ataxia center for the Rare Diseases Clinical Research Network is to continue recruiting patients and to identify new genes in an effort to improve diagnosis and treatment.

Designated the episodic ataxia center for the Rare Diseases Clinical Research Network sponsored by the National Institutes of Health, the investigators are referred patients with episodic ataxia from across the country. The network researchers have recruited a large number of patients with episodic ataxia, yet only less than a third has been genetically characterized. The main goal is to continue to recruit patients, to apply state of the art research strategies to identify new EA genes, and to understand how mutations lead to symptoms. These efforts will improve the diagnosis and treatment of episodic ataxia and related disorders.
Ataxia; Clinical Research; Genetics
Spinal Cord Injury: Targeting Local Inhibition to Improve Outcome University of California San Francisco: Arnold Kriegstein

Using a novel stem cell transplantation strategy, the researchers aim to help people struggling with involuntary muscle spasms and other problems resulting from chronic spinal cord injury.

There are an estimated 250,000 individuals who currently live with disability associated with chronic spinal cord injury. This proposal addresses a novel stem cell transplantation strategy to ameliorate bladder dysfunction and involuntary muscle spasms that accompany chronic spinal cord injury. A long-term goal of these studies is to translate this effort to the spinal cord injured patient, with a specific focus on improving bladder function and reducing muscle spasms, both of which can profoundly affect quality of life.
Trauma (Head and Spine); Neurodegeneration; Regenerative Medicine; Spinal Cord Injury; Stem Cell Research (Nonembryonic - Non-Human); Transplantation
Spinal Adenosine Modulator: Enduring Anti-inflammatory Action in Neuropathic Pain University of Colorado at Boulder: Linda Watkins

This project is aimed at providing the 'proof-of-concept' for using a new therapeutic approach for chronic pain.

This proposal builds from the discovery that a single intrathecal administration of adenosine 2A (A2A) agonists produces a remarkably enduring reversal of neuropathic pain of at least several weeks, with evidence to date suggestive that such drugs may 'reset' chronically activated spinal glial cells to an overtly anti-inflammatory state that suppresses pain. This project is aimed at providing the 'proof-of-concept' for using A2A agonists as a new therapeutic approach for chronic pain.
Neurodegeneration; Neuropathy; Pain (Chronic)
CNS Inflammation in Nervous and Mental Disease University of Connecticut School of Medicine: Joel S. Pachter

This work investigates whether cell-specific release of the chemokine CCL2 can regulate discrete aspects of neuroinflammation in an animal model for multiple sclerosis.

In multiple sclerosis and other inflammatory disorders of the central nervous system, white blood cells leave the circulation and invade the brain and/or spinal cord, where they cause significant destruction of nerve cells leading to severe difficulties in movement. These white blood cells are stimulated to act by a special class of substances in the body called 'chemokines,' which instruct these cells to exit the blood and then enter and move through the nervous system. The broad objective of this project is to understand how one such chemokine, in particular, executes its functions.
Multiple Sclerosis; Autoimmune Disease; Neurodegeneration
Clinical Research Consortium for Spinocerebellar Ataxias University of Florida: Tetsuo Ashizawa

To understand spinocerebellar ataxias (SCAs) better, this project will establish a consortium for multidisciplinary clinical studies of new treatment options.

Spinocerebellar ataxias (SCAs) are inherited neurological diseases which relentlessly worsen over time, leading to severe disability or death. This study will focus on four subtypes of SCAs, SCA 1, 2, 3 and 6, in which investigators have made major advances in understanding the disease mechanisms and started contemplating novel treatments. This research will establish a clinical research consortium for SCA (CRC-SCA), which will provide multidisciplinary infrastructure to bring these novel treatment ideas to bedside.
Ataxia; Clinical Research; Clinical Trials; Genetics; Neurodegeneration
Translating CNS Therapies for the NCLs from Rodent Models to Humans University of Iowa: Beverly L. Davidson

In this translational research program investigators are using gene therapies in animal models of childhood-onset neurological diseases such as Batten disease.

This project will deal with testing the safety and efficacy of gene therapies designed to correct central nervous system manifestations in a dog model of childhood-onset neurological diseases. These studies are an important step in a translational research program encompassing established investigators and new trainees at the University of Iowa and the University of Missouri, which builds upon preliminary work in rodent models showing robust improvements in behavioral manifestations and neuropathology shortly introduction of therapeutic vectors.
Batten Disease; Gene Therapy; Genetics; Neurodegeneration; Pediatric Studies; Prevention
RNA Interference Therapy for Huntington's Disease: Studies in Non-human Primates University of Iowa: Beverly L. Davidson

In this work scientists are testing gene therapies to treat Huntington's disease, hoping to move new discoveries from the animal models in the lab into the clinic.

In this study involving Huntington's disease, the goal is to test the safety and efficiency of gene therapies designed to treat the fatal neurogenetic disorder in a clinical relevant model, the nonhuman primate. Experiments are designed to test questions relevant to moving therapeutic gene silencing strategies from efficacy studies in rodent models to the clinic, and to address important issues regarding this therapy for Huntington's disease. This work is a collaborative effort between laboratories at University of Iowa and Oregon National Primate Research Center at the Oregon Health Sciences University.
Huntington's Disease; Aging; Neurodegeneration; Gene Therapy; Genetics
High-Throughput Genetic & Small-molecule Screening for Therapeutic Modifiers University of Iowa: Kevin P. Campbell

Using mouse models, this work will identify new gene mutations contributing to muscular dystrophy and to search for compounds that may provide new treatment strategies.

Muscular dystrophies are a diverse set of inherited diseases characterized by progressive skeletal muscle weakness and wasting. Dystroglycan, a cell surface protein, requires extensive modification to serve as a link between the intracellular and extracellular cellular support network in muscle such that, when disrupted, it results in several forms of muscular dystrophy. This proposal is designed to identify new gene mutations that can cause these types of muscular dystrophy, discover small molecules that can improve dystroglycan function, develop needed mouse models of the disease and to validate both newly identified and currently known treatment strategies.
Genetics; Muscular Dystrophy; Neurosciences; Prevention
Vascular Responses as Therapeutic Targets after SCI University of Louisville: Theo Hagg

This research aims to develop drugs that rescue blood vessels damaged by spinal cord injury, head trauma and stroke.

These studies will help develop drugs that rescue injured blood vessels, which is relevant to disorders such as spinal cord and head injury and stroke.
Spinal Cord Injury; Trauma (Head and Spine); Neurodegeneration
Family Study of Stroke and Carotid Atherosclerosis University of Miami School of Medicine: Ralph L. Sacco

This study focuses on gene-related cerebrovascular risk factors that could help in predicting stroke risk.

The goal of this study is to identify genetic determinants of cerebrovascular risk phenotypes that are precursors to stroke, to assist in stroke risk prediction.
Stroke; Aging; Clinical Research; Genetics; Human Genome
Unraveling Mechanisms of Niemann-Pick C Neuropathology with Mouse Models University of Michigan at Ann Arbor: Andrew P. Lieberman

This work examines neurodegeneration in Niemann-Pick C disease and related lipid storage diseases.

The studies will help unravel the mechanisms of neurodegeneration in Niemann-Pick C disease. Understanding these pathways may lead to the identification of novel therapeutic targets for treating patients with this disorder and related lipid storage diseases.
Niemann-Pick C disease; Biotechnology; Genetics; Neurodegeneration; Pediatric Studies
Biomarkers in Diabetic Neuropathy University of Michigan at Ann Arbor: Eva L. Feldman

This project searches for signs of the onset and progression of nerve damage, a frequent complication of diabetes.

The most common complication of diabetes is peripheral neuropathy (DN). The identification of DN biomarkers would greatly enhance understanding of early events in this complication and could be used to predict its development and rate of progression. The investigators hypothesize diabetes directly affects peripheral nerve gene expression and that these data will aid in identification of DN biomarkers. Microarray analyses will compare changes in gene expression between human sural nerve biopsies and BKS-db/db mice, a well-researched model of type 2 diabetes. These data will be used to identify dysregulated intracellular pathways that would result in detectable DN biomarkers in serum or urine and changes in expression following treatment in animal models.
Neuropathy; Diabetes; Aging; Biotechnology; Neurodegeneration; Pain (Chronic)
Stem Cell Derived Neurons and Inherited Epilepsy University of Michigan at Ann Arbor: Miriam H. Meisler

Through a new technique of deriving neurons from skin cells, researchers are investigating severe myoclonic epilepsy in infancy (SMEI) and other neurological disorders in molecular detail and hope to develop screens for drugs to prevent disease progression.

Epilepsy is a common and debilitating neurological disorder, with a frequency of approximately 1 in 1,000 individuals. Many cases are resistant to currently available therapies. The severe genetic disorder SMEI has childhood onset and rapid progression and does not respond to treatment. Until now, it has not been possible to study the effects of SMEI mutations on nerve cells, because brain tissue from patients is not available for study. However, the newly developed technique of deriving neurons from skin biopsies means that SMEI and other neurological disorders can now be studied in molecular detail. The investigators have succeeded in generating neurons from a patient with SMEI. These cells will be analyzed to determine the effects of the underlying mutation. After the molecular features of the abnormality are characterized, it may become possible to use these cultured neurons to screen for drugs which can prevent the progression of this disabling disease.
Epilepsy; Genetics; Clinical Research; Regenerative Medicine; Stem Cell Research (Nonembryonic - Human)
Using Transport to Map the Brain University of New Mexico: Elaine L. Bearer

Through advanced imaging technology, scientists will map brain circuits in mouse models to study Down syndrome, Alzheimer's disease, and other neurological disorders.

Mental retardation and senility may involve the same circuits within the brain: connections between the hippocampus and basal forebrain. Manganese enhanced magnetic resonance imaging (MEMRI) allows us to observe the anatomy and activity within this circuit in living brains. The investigators propose to develop and apply this technology to map this important memory circuit in mouse models towards gaining an understanding of two frequently occurring diseases: Down syndrome and Alzheimer's disease.
Aging; Alzheimer's Disease; Diagnostic Radiology; Down Syndrome; Mental Retardation; Neurodegeneration
Matrix Metalloproteinases and the Blood-Brain Barrier University of New Mexico: Gary Allen Rosenberg

The investigators will focus on enzymes involved in controlling the structure of blood vessels in the brain involved in cognitive impairment in the elderly.

This novel proposal will evaluate the contribution of enzymes that regulate the structure of brain blood vessels to cognitive impairment in the elderly.
Stroke; Aging
Quantitative Genetic Study of Seizures University of Pennsylvania: Thomas N. Ferraro

This project involves identifying genes in mice that determine susceptibility to experimentally- induced seizures, knowledge that can ultimately be applied to human patients with epilepsy.

This project involves identification of genes in mice that determine their susceptibility to experimentally-induced seizures. Whereas the short term goal involves the identification of seizure susceptibility genes, longer term goal is to understand how they influence seizure susceptibility. Ultimately, knowledge gained from mouse studies will be applied to human patients with epilepsy and epilepsy genetics research. Since the laboratory is dedicated to translational research, results from mice will be used directly to inform clinical studies. The study investigators maintain repository of 1000+ DNA samples from patients with common forms of epilepsy and use them to investigate genes suggested by mouse research. Ultimately, a better understanding of biological basis of seizure susceptibility in mice and genetic predisposition to epilepsy in humans will facilitate development of novel and more effective therapeutic options.
Epilepsy; Genetics; Human Genome; Neurodegeneration
Multi-Center Validation of Biomarkers for Motor Neuron Disease University of Pittsburgh: Robert P. Bowser

The project goal is to find specific biomarkers to help in diagnosing amyotrophic lateral sclerosis (ALS).

The overall goal of the proposed study is to validate specific biomarkers for amyotrophic lateral sclerosis (ALS). ALS is a fatal motor neuron degenerative disease that can strike adults of any age, yet investigators know little about its causes and cannot rapidly diagnose ALS. The validated protein and antibody based biomarkers for ALS will create quick diagnostic tests for ALS.
Amyotrophic Lateral Sclerosis (ALS); Brain Disorders; Clinical Research; Neurodegeneration; Neurosciences
a-Synuclein and Dopamine: Implications of Parkinsonism University of Pittsburgh: Ruth G. Perez

This project examines alpha-synuclein, a protein linked to neuronal cell loss in Parkinson's disease.

The goal of this project is to understand the link between neuronal cell loss and alpha-synuclein to ultimately identify points of intervention for treating Parkinson's disease.
Parkinson's Disease; Neurodegeneration
Genotype and Metabolic Phenotype in Glioblastoma University of Texas SW Medical Center/Dallas: Elizabeth A. Maher

The investigator will examine metabolic pathways in glioblastoma, a lethal brain cancer, for targets that could lead to new therapeutics.

Gliobastomas are the most common primary brain tumor and are among the deadliest of human cancers. The metabolism of the cells is much higher than normal cells and, like many cancers, represents a possible target for new drugs in cancer therapy. This proposed research will dissect the metabolic pathways that are abnormal in glioblastoma in a concerted effort to develop new therapies quickly.
Brain Cancer; Clinical Research; Diagnostic Radiology; Genetics; Orphan Drug
Development of Small Molecule Orexin Receptor Agonists for Treating Narcolepsy University of Texas SW Medical Center/Dallas: Jef DeBrabander

The investigators will screen compounds that could become better drugs to treat narcolepsy, a serious sleep disorder.

The investigators propose development of drug-like preclinical candidates for the treatment of narcolepsy, a debilitating disorder affecting approx 200,000 Americans. Current treatments for narcolepsy exhibit various undesirable side-effects and ineffective for correcting the underlying neurochemical deficits. This proposed research is highly relevant, as it seeks to translate the finding that orexin deficiency is at the root of narcolepsy, into a drug candidate designed to replace endogenous orexin, and as such provide a potential cure for human narcolepsy.
Sleep Research; Orphan Drug
Enhancing Progranulin Expression - a Therapy for Frontotemporal Dementia University of Texas SW Medical Center/Dallas: Joachim J. Herz

This project aims to develop and conduct early tests on a combined drug therapy to prevent or delay frontotemporal dementia onset.

One form of frontotemporal dementia (FTD) is frequently caused by nonsense mutations in a presumed signaling protein, Progranulin (GRN). This project aims to develop and perform preclinical testing of a combinatorial drug treatment approach that aims at restoring normal GRN levels and function, as an approach to prevent or delay FTD onset.
Frontotemporal Dementia (FTD); Genetics; Neurodegeneration
Modeling Neurodegeneration and Adrenoleukodystrophy in Drosophila University of Utah: Anthea Letsou

Scientists aim to develop a new animal model to help the search for treatment of adrenoleukodystrophy (ALD).

The purpose of this study is to fully characterize a newly developed animal model of adrenoleukodystrophy (ALD). This model promises to be particularly significant and powerful because it provides a model organism platform for the identification of drugs that will facilitate treatment of this devastating disease.
Adrenoleukodystrophy; Genetics; Neurodegeneration
Hydrocephalus Clinical Research Network: a Consortium for Pediatric Hydrocephalus University of Utah: John Kestle

Scientists will organize a coordinated network of investigators working on pediatric hydrocephalus, or brain swelling in children.

Pediatric hydrocephalus is a very common problem resulting in almost 40,000 hospital admissions, more than 400,000 hospital days and $2 billion in hospital charges in 2003. With very few exceptions, clinical research has been conducted at a single center with retrospective data, which do not allow strong conclusions about treatment efficacy. This proposal is to establish a coordinated network to identify the areas of most urgent need in hydrocephalus research and conduct prospective studies to solve these problems. The network has developed a Core Data Project and 3 focused studies, which will generate pilot data needed to plan prospective trials in the future.
Hydrocephalus; Clinical Research; Comparative Effectiveness Research; Pediatric Studies; Assistive Technology; Bioengineering
Decompressive Craniotomy Versus Medical Therapy for Refractory Intracranial Hypertension University of Utah: Raminder Nirula

The research goal aims at identifying improved treatment strategies to manage patients with moderate to severe traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem in the United States with approximately 1.4 million people sustaining a traumatic brain injury annually. Of these, 50,000 die and 235,000 are hospitalized yearly leading to direct medical costs; as a result of lost productivity the cost is an estimated $60 billion in the United States in the year 2000. Identifying improved treatment strategies to manage patients with moderate to severe traumatic brain injury is necessary and would have tremendous public health impact.
Trauma (Head and Spine); Clinical Research; Comparative Effectiveness Research
Neuropsychological Progression of New Onset Epilepsy University of Wisconsin Madison: Bruce P. Hermann

This project explores brain development in children with new onset epilepsy to gain a better understanding of risk factors for the disease.

The goal of this application is to further define the abnormalities in brain structure, cognition and psychopathology during development in children with new onset epilepsy. The proposed work has tremendous clinical significance as it may identify risk factors that enable the development of prognostic measures in these children.
Epilepsy; Clinical Research; Neurodegeneration; Pediatric Studies
Untangling Amyloid Plaques With Proteases Washington University: Jin-Moo Lee

The study seeks to determine if an enzyme causes the build up of amyloid plaques thought to cause Alzheimer's and related disorders); if found, study results may lead to new therapeutics.

This project will test the hypothesis that MMP-9, secreted by astrocytes surrounding amyloid plaques, regulates amyloid plaque growth/regression by degrading soluble and fibrillar A² and amyloid fibrils of which plaques are comprised. If this is true, potential targets for intervention to degrade plaques may be identified.
Alzheimer's Disease; Aging; Genetics; Neurodegeneration
Mechanisms of Deep Brain Stimulation Washington University: Joel S. Perlmutter

This research aims to understand how to optimize the benefit of electrical stimulation treatments for Parkinson's disease.

These studies will potentially provide insights into the mechanisms underlying the clinical effects of Deep Brain Stimulation (DBS) for Parkinson's disease, thereby helping to optimize benefit and minimize side effects.
Parkinson's Disease; Clinical Research; Neurodegeneration; Bioengineering
Activity-Dependent Gene Expression in Human Epilepsy Wayne State University: Jeffrey A. Loeb

The researchers are building an animal model for human epilepsy to better understand the disorder and to develop diagnostic and therapeutic interventions.

The goal of this project is to develop an animal model for human epilepsy, to better understand the molecular pathways underlying epilepsy, and to develop diagnostic and therapeutic interventions.
Epilepsy; Genetics; Neurodegeneration
Gene Discovery in Recessive Structural Brain Disorders through Whole Exome Sequence Yale University: Murat Gunel

The project involves sequencing exons (the 1 percent of the human genome which codes for proteins) from 250 families, to discover genes that cause brain malformations linked to epilepsy, autism and neuropsychiatric disorders.

Structural brain abnormalities are a major cause of epilepsy, developmental delay and mental retardation. More subtle forms are associated with other neurodevelopmental disorders, including autism. The researchers propose to use exomic sequencing to discover genes that cause brain malformations in a highly selective cohort of 250 independent families, confirmed to be consanguineous by high density SNP genotyping. Discovery of genes causing these abnormalities will allow fundamental mechanistic insights into brain development and potentially allow new therapeutic approaches to these and related neuropsychiatric disorders.
Epilepsy; Autism; Mental Retardation; Clinical Research; Genetics; Pediatric Studies
Molecular Determinants of Adult CNS Axonal Growth Yale University: Stephen M. Strittmatter

The researchers hope to develop new strategies to treat neurological conditions by identifying the function of proteins that block nerve regeneration.

By identifying the function of proteins that block regeneration, the investigators seek to develop therapeutics that will promote rehabilitation and recovery for multiple neurological conditions.
Trauma (Head and Spine); Neurodegeneration; Rehabilitation; Spinal Cord Injury

Last updated July 27, 2010