National Institute of Mental Health

The National Institute of Mental Health (NIMH) is one of 27 components of the National Institutes of Health (NIH), the Federal government's principal biomedical and behavioral research agency. NIH is part of the U.S. Department of Health and Human Services.

Mission

The NIMH mission is to reduce the burden of mental illness and behavioral disorders through research on mind, brain, and behavior. This public health mandate demands that we harness powerful scientific tools to achieve better understanding, treatment, and eventually, prevention of these disabling conditions that affect millions of Americans. To fulfill its mission, the Institute conducts research on mental disorders and the underlying basic science of brain and behavior; supports research on these topics at universities and hospitals around the United States; collects, analyzes, and disseminates information on the causes, occurrence, and treatment of mental illnesses; supports the training of more than 1,000 scientists to carry out basic and clinical research; and communicates information to scientists, the public, the news media, and primary care and mental health professionals about mental illnesses, the brain, behavior, mental health, and opportunities and advances in research in these areas.

Technology Disciplines

Medical-Health

Technologies

Displaying 1 - 10 of 35

A Fold-Back Diabody Format for Diphtheria Toxin-Based Immunotoxins That Can Increase Binding and Potency

Description:

production process of the fold-back immunotoxin can be used to scale up for GMP production.

Abstract

NIH inventors, in collaboration with Scott and White Memorial Hospital inventors, have developed new immunotoxins comprising a mutant diphtheria toxin linked to an anti-prostate specific membrane antigen (PSMA) fold-back diabody. The fold-back diabody construct has a shortened linker region between the heavy and light chains of the antibody variable domain. This construct allows interactions between the longer-linked variable domains while preventing interactions between the shorter-linked variable domains. This results in increased efficiency of epitope recognition and delivery to the appropriate target cells. These immunotoxins can be used for the treatment of cancers that overexpress PMSA, with specific application against prostate cancer.

Benefits

Increased potency of 10-40-fold resulting from the use of the fold-back diabody construct. - First treatment with applications to metastatic prostate cancer. - Pichia pastoris production process of the fold-back immunotoxin can be used to scale up for GMP production.

Details

Internal Lab Reference ID	E-268-2007/0
Patent Number	PCT/US2008/009321 US Application No. 60/953,416 US Application No. 12/671,629
Inventors	David Neville Jr (NIMH)

A Neuronal Avalanche Size (NAS) Assay to Screen for Cognitive Enhancers and Anti-Epileptics

Description:

screen to assess drugs with the ability to enhance cognitive function, and ultimately, relieve cognitive defects associated with psychiatric illnesses and neurological disorders.

Abstract

Currently available methods of detecting and measuring EEG activity only crudely classify normal and abnormal activity or distinguish epileptic activity early in the onset of its deviation from normal activity. Available for licensing are methods for recognizing a new pattern of EEG activity called neuronal avalanche size (NAS) that has been correlated with cognitive function and epilepsy. The NAS uses extracellular field potentials to measure the distribution of synchronized neurons in the cortex (neuronal avalanches) and thus the state of the cortical network. When the avalanche size reaches a power law with a slope of -3/2, the system is in the critical state and the cortical network is functioning optimally to spread information throughout the network. If the system slope deviates from -3/2, the system is outside the critical state and is either epileptic or sub-critical. In animal studies measurement of NAS quantified a drug’s potential to increase cognitive functioning and induce or reduce epilepsy. The NAS assay may thus enable high-throughputin vitroscreens to select anti-epileptics and cognitive enhancing drugs for continued drug development. Because avalanches represent scale-invariant dynamics they can also be recorded using surface (EEG) electrodes. This technology may thus be useful in assessing cognitive function, epileptic pathology and in selecting and monitoring drug therapy for epileptic patients.

Details

Internal Lab Reference ID	E-294-2005/1
Patent Number	8,548,786issued 2013-10-01 PCT Application No. PCT/US2006/031884
Inventors	Dietmar Plenz (NIMH)

Available Technology

Abstract

This CDC-developed technology relates to improved, full-face flushed-seal personal respirators for lowering costs, improving user mobility, and ensuring occupational health and safety. Currently, the most common type of respirator in use, the negative pressure respirator, seals to a user’s face so that inhaled air is pulled through a purifying filter by inhalation-generated negative pressure; the weakest link in this type of respirator is typically the seal at the face-to-mask interface. When there is face-seal leakage, toxic air will be drawn into the facepiece of the respirator and inhaled by the wearer, though designers and engineers of respirators attempt to minimize this face-seal leakage. Over the last several decades, facepiece design has been optimized by this design approach so that the ambient leakage of half-facepiece respirators and full-facepiece respirators are 10% and 2%, respectively. This technology incorporates an additional element to reduce face-seal leakage and therefore increases user protection. In the respirator described by this technology, a primary sealing element is situated adjacent to the user's breathing space and a secondary sealing element. Exhaled air (i.e., clean air obtained by filter passage) is passed from the breathing space into a flushing channel formed between the primary and secondary seals. If there is leakage in the primary seal, air from this flushing channel leaks into the breathing space rather than toxic, ambient air. Air within the flushing channel will predominately be air that has already passed through the filtering elements. The present invention provides, therefore, an inexpensive respirator which provides significantly more protection than conventional negative-pressure respirators. Further, at present the only alternative respirator types that offer such great levels of user protection are expensive, require heavy batteries and blowers or an airline, and have a limited service life.

Benefits

Inexpensive to implement - Provides significantly more protection than conventional negative-pressure respirators - Unlike PAPR devices, no heavy, mobility-limiting battery packs are required for this technology; no battery recharge time or noisy blowers with this respirator technology - Compared to "air-line" respirators, this technology is significantly less expensive to purchase and maintain and does not limit the range of a user’s mobility

Details

Patent Number	7877340
Inventors	Charles A Gentile
Patent Issue Date	Jan 25, 2011

Documents

- 5093.pdf (format PDF / 1 MB)

Beta-Amyloid and Tau Fibril Positron Emissions Tomography (PET) Imaging Agents

Description:

In vitro data available

Abstract

The invention relates to two novel classes of compounds useful as radioligands for in vivo imaging of beta-amyloid fibrils, peptides and plaques in humans. Beta-amyloid peptide deposition in the brain is a pathological feature of Alzheimer's disease (AD). Early detection of beta-amyloid load in patients with suspected AD is vital to initiating early treatment, which can improve cognitive function and quality of life for many patients. The invention describes novel derivatives of imidazopyridinylbenzeneamine (IMPY) and benzothizolylbenzeneamine (BTA), which demonstrate high in vitro binding affinity to human beta-amyloid. The difference between existing IMPY compounds and the novel derivatives is the substitution of an aryl halide with an aryl thioether group and replacement of a sulfur group of the pyridine ring with a nitrogen group. The new classes of compounds have the potential of providing improved amyloid imaging agents for Positron Emission Tomography (PET) with higher specificity for amyloid, low background noise, better entry into the brain and improved labeling efficiency.

Benefits

Specificity

Details

Internal Lab Reference ID	E-156-2006/0
Patent Number	12/293,340 PCT Application No. PCT/US2007/066939 U
Inventors	Lisheng Cai

Beta-Amyloid and Tau Fibril Positron Emissions Tomography (PET) Imaging Agents

Description:

In vitro data available

Abstract

Benefits

Specificity

Details

Internal Lab Reference ID	E-156-2006/0
Patent Number	12/293,340 PCT Application No. PCT/US2007/066939 US Application No. 60/793,807
Inventors	Lisheng Cai

Beta-Amyloid and Tau Fibril Positron Emissions Tomography (PET) Imaging Agents

Description:

Abstract

Benefits

Specificity

Details

Internal Lab Reference ID	E-156-2006/0
Patent Number	8,703,096issued 2014-04-22 US Application No. 12/293,340 PCT Application No. PCT/US2007/066939 US Application No. 60/793,807
Inventors	Robert Innis (NIMH) , Victor Pike (NIMH) , Lisheng Cai (NIMH)

Cannabinoids As Neuroprotectants

Description:

Abstract

This technology describes the neuroprotective properties of cannabidiol(CBD), 2-[3-Methyl-6-(1-methylethenyl)-2-cyclohexen-1yl]-5-pentyl-1,3-benzenediol. Cannabidiol is a neuroprotective cannabinoid that does not possess the psychoactive qualities which have previously hampered the development of cannabinoid-based therapeutics. Cannabidiol is an effective blood-brain barrier permeable antioxidant, that is more potent than either tocopherol or ascorbate. As reported in PNAS 95, 8268-73 (July 1998), CBD can protect neurons from both glutamate and free radical induced toxicity. It is believed that CBD may present a viable alternative for treatment of ischemia or physical traumas. Aidan Hampson (NIMH)➽ more inventions... Julius Axelrod (NIMH)➽ more inventions... Maurizio Grimaldi (NINDS)➽ more inventions... U.S. Pat:6,630,507issued 2003-10-07 US Application No. 60/095,993 PCT Application No. PCT/US99/08769 US Application No. 09/674,028 Jennifer Wong, M.S. Email:[email protected] Phone: 301-480-4821 E-287-1997/0 Updated:Nov 9, 2015

Details

Internal Lab Reference ID	E-287-1997/0 Updated:Nov 9, 2015
Patent Number	6,630,507issued 2003-10-07 US Application No. 60/095,993 PCT Application No. PCT/US99/08769 US Application No. 09/674,028
Inventors	Aidan Hampson

HIV-Dependent Expression Vector

Description:

This invention provides a DNA construct that can be useful for both diagnostics and AIDS therapeutics. The construct can be incorporated into a retrovirus or into a cell line. This construct mediates the expression of a selected gene in the presence of HIV replication, but is silent in the absence of HIV. The cell line with the incorporated construct can be used as an indicator line for the presence of replication-competent HIV. The virus containing the construct can be used to co-infect a population of HIV-infected cells. If the construct-encoded gene is a reporter, it would specifically identify cells that are infected with HIV. If the construct-encoded gene is a cytotoxin, it would specifically kill cells that are HIV-infected. This invention may offer a novel approach to HIV elimination, as well as detection of HIV infected cells or the presence of cell-free infectious HIV.

Abstract

Details

Internal Lab Reference ID	E-276-2003/0
Patent Number	10/574,031 US Application No. 60/507,034
Inventors	Jon Marsh

Immunotoxin with in-vivo T cell Suppressant Activity

Description:

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of autoimmune diseases and T cell malignancies. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced inPichia pastoris. Data are available in transgenic animals expressing human CD3epsilon which supports the effects of the immunotoxin against T cells.

Abstract

Benefits

Specificity of the immunotoxin avoids the killing of non-T cells, reducing side-effects associated with other mechanisms of treatment (e.g., radiation and cyclophosphamide) such as infection and induced malignancy. -A GMP production process has already been successfully implemented, and patient doses are available. -All testing required for an FDA issued IND has been completed, allowing faster evaluation of the efficacy of the invention.

Details

Internal Lab Reference ID	E-012-1991/0 Updated:Nov 9, 2015
Patent Number	13/443,779 US Application No. 07/907,409 PCT Appli
Inventors	David Neville Jr

Immunotoxin with in-vivo T cell Suppressant Activity

Description:

Abstract

Benefits

Details

Internal Lab Reference ID	E-012-1991/0 Updated:Nov 9, 2015
Patent Number	13/443,779 US Application No. 07/907,409 PCT Application No. PCT/US92/00813 US Application No. 60/039,987 PCT Application No. PCT/US98/04303 US Application No. 10/435,567 Foreign rights are also available.
Inventors	David Neville Jr

Facilities

Displaying 1 - 6 of 6

Laboratory of Brain and Cognition (LBC)

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The Laboratory of Brain and Cognition (LBC) is a branch of the Division of Intramural Research Programs ( DIRP ) at the National Institute of Mental Health ( NIMH ). The NIMH is part of the National Institutes of Health ( NIH ), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services ( DHHS ). The LBC consists of four Sections, headed by Dr. Leslie G. Ungerleider (Section on Neurocircuitry), Dr. Alex Martin (Section on Cognitive Neuropsychology), Dr. Peter A. Bandettini (Section on Functional Imaging Methods), and Dr. Chris I. Baker (Section on Learning and Plasticity), with Dr. Ungerleider as the Laboratory Chief. The LBC is a highly interactive and collegial environment, in which collaborations within and across the Sections are encouraged. There are three main themes of research in the LBC: Physiology and Behavior of Nonhuman Primates - Dr. Ungerleider's Section has long been devoted to establishing the links between neural structure and cognitive function, especially in the visual modality. Her early work was devoted to anatomical tracing techniques in macaque monkeys. By the mid-1990s, she and others had succeeded in mapping much of the monkey extrastriate visual cortex and had outlined some of the major functional systems. With the advent of functional brain imaging in humans, Dr. Ungerleider began the study of human cortex, using first PET and then fMRI. Monkey work has guided many of her hypotheses in the human imaging studies. Dr. Ungerleider's monkey program includes monkey fMRI and electrophysiological studies in order to carry on parallel studies in humans and monkeys for which her lab is recognized. Human Cognitive Neuroscience and Functional Brain Imaging - Four Sections in the LBC, headed by Drs. Ungerleider (sNC), Martin (sCNP), Bandettini (sFIM), and Baker (sLP) plan and conduct research on the functional organization of the human brain using functional magnetic resonance imaging (fMRI). The primary focus is on the visual modality as a model system for investigating perception, attention, learning, memory, decision-making, and the representation of semantic knowledge. Functional brain imaging studies are motivated by both the anatomy and physiology of the visual system in non-human primates and cognitive impairments produced by focal brain lesions in humans, as well as by models from cognitive science. Functional Imaging Methods - The long-term research goal of Dr. Bandettini's Section is the development and implementation of advanced fMRI methods towards an increased understanding of the functional organization and physiology of the human brain, and ultimately increased clinical utility. A major focus has been to understand the relationship between neuronal activity and fMRI signal changes, and to explore new methods for extraction of neuronal information from resting and active fMRI time series. sFIM research has been balanced across the four themes of methodology, technology, interpretation, and applications. In recent years, this focus has shifted towards more interpretative and methodological advancements.

Laboratory of Cellular and Molecular Regulation

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This Laboratory plans and conducts research on the anatomical, cellular, physiological, pharmacological, biochemical, and molecular bases of the expression and regulation of brain functions.

Laboratory of Molecular and Cellular Neurobiology (LMCN)

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Neurotransmitters such as dopamine and glutamate are rapidly removed from the synaptic cleft after release, primarily through the actions of neurotransmitter transporters. These integral membrane proteins function to clear neurotransmitters that have been released from both synaptic and extrasynaptic sites. This uptake process is not only essential for the termination of neurotransmission, but also serves to reestablish the intracellular levels of the neurotransmitters for subsequent release. Neurotransmitter transporters are secondary active transporters. By coupling the movement of Na + ions down their electrochemical gradient, these carriers can transport their specific substrates against an energy barrier into the cell. In addition to their transport function, some of these carriers also act as selective anion channels. Using electrophysiological, cell biological, molecular genetic and biochemical techniques combined with transgenic animal models, our laboratory investigates the structure-function relationships, pharmacology, cellular regulation and molecular interactions of the members of the SLC1 and the SLC6 families. The SLC1 family encompasses the five subtypes of the excitatory amino acid transporters (EAATs), and the SLC6 family includes the Na +-dependent transporters for dopamine, serotonin and noradrenaline, also known as the biogenic amine transporters. These two families of neurotransmitter transporters have been implicated in a number of neuropsychiatric conditions including Parkinson's Disease, primary mood disorders, drug addiction, schizophrenia, obsessive compulsive disorder (OCD), and attention deficit hyperactivity disorders (ADHD, ADD). In addition, biogenic amine neurotransmitter transporters are the primary targets for therapeutic antidepressants known as reuptake inhibitors, for psychostimulants such as cocaine and amphetamines and for methylphenidate, which is used to treat ADHD. Thus, our aim to understand the function and regulation of these multifunctional CNS transporters is ultimately linked to the NIMH mission of providing improved prevention, diagnosis and treatment of mental illnesses.

Laboratory of Neuropsychology (LN)

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The Laboratory of Neuropsychology conducts basic research on brain mechanisms of perception, attention, memory, emotion, motivation, and motor function. The Laboratory of Neuropsychology is part of the Intramural Research Program of the National Institute of Mental Health. It is located on the main campus of the National Institutes of Health (NIH) in Bethesda, MD, USA.

Section on the Neurobiology and Treatment of Mood Disorders (SNMD)

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The major goal of the SNMD is to conduct therapeutic studies on treatment-resistant depression, with a more recent extension to patients with suicidal ideation and behavior. The major focus of our clinical research is treatment-resistant depression. SNMD is housed in the Mood Disorders Research Unit, 7SE north of the NIH Clinical Center, a state-of-the art facility which currently has 12 inpatient beds designated for patients with mood disorders of which Dr. Zarate is the Unit Chief. Clinical staffing includes a 24 hour, 365 day on-call psychiatrist, experienced nurse clinicians, etc. Our ability to study patients for long periods of time, over nights and weekends in both the drug free as well as post-treatment states provides a unique opportunity for comprehensive evaluation that would not be possible in the extramural world. The program attempts to identify reasons for and ameliorate the high failure rate in recent pharmacologic trials of mood disorders including patient heterogeneity, inadequate diagnostic and response biomarkers, incorrect dose range, high placebo response rates, inadequate trial designs, patient and investigator expectation biases, lack of target engagement, and a host of operational issues. By avoiding many of these situations, we can improve the feasibility and acceptability by advancing early proof-of-concept clinical trials designs that can be subsequently translated to our extramural partners for larger effectiveness and efficacy studies. In addition to collaborative efforts designed to cover the full range of biologic pathways underlying mood disorders, we have focused our research on treatment-resistant depression in two major research areas: (1) neuroimaging; and (2) biomarkers of mood disorders and treatment response. The NIMH DIRP Cores have also provided an ideal source of expertise in our neuroimaging studies. Our research has also benefited enormously from both the NIH Clinical Center facilities and the DIRP CORE facilities (e.g., sMRI, fMRI, PET, PSG, MEG, MRS, etc).

The Experimental Therapeutics and Pathophysiology Branch (ETPB)

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The overarching goals of the current (ETPB) are: (1) to provide administrative support for our Section (SNMD); (2) to maintain a common screening program for the Division of Intramural Research Program (DIRP) studies on mood and anxiety disorders; and (3) to support clinical and research training. The Screening Program (01-M-0254) provides oversight, training, and quality control of administration of a range of structured diagnostic and dimensional measures of psychopathology. Aside from extensive clinical measures, the major data components that are centralized in the program include: (1) CTDB-Clinical trials database; (2) BioBNK that contains a diverse set of biologic measures; and (3) MAP-R (Mood and Anxiety Disorders Repository protocol) of neuroimaging data. The clinical measures collected include comprehensive diagnostic interviews including history of suicide attempts and ideation, stress/trauma, sleep problems, temperament, psychosis, medical conditions, as well as dimensional measures of the core features of mood and related disorders including positive and negative affect, arousal/regulatory systems and cognitive function.