This invention relates to a novel mouse model that permits temporal and spatial inactivation of the oxytocin receptor. Oxytocin is a neurohormone that has been associated with human diseases such as autism and schizophrenia. The use of animal models to study oxytocin disease progression has been invaluable. However, existing mouse models have been limited to knockouts which leads to early mortality. Researchers at the National Institute of Mental Health (NIMH) generated the conditional oxytocin receptor knockout mice using the Cre-loxP and FLP-FRT systems.

Gene therapy and gene transfer have recently been recognized as effective therapeutic tools to combat diseases. Accordingly, market demands for vectors and carriers to facilitate such interventions have surged in recent years. Retroviral vectors provide an efficient and safe means of gene transfer to eukaryotic cells. The present invention relates to genetic engineering involving retrovirus packaging cells that produce retroviral vectors.

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 in Pichia pastoris.

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts.

The invention concerns immunotoxins and methods of making the immunotoxins. Targeting of the immunotoxins occurs 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. As a result, the immunotoxin can be used to treat autoimmune disease, malignant T cell-related cancers, and graft-versus-host disease.

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 invention offers technology to help treat certain brain diseases, such as Alzheimer's disease and Parkinson's, and may lead to more effective and personalized treatments. P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established/prospective chemotherapeutics (a phenomenon known as multidrug resistance; MDR).

With respect to quantification of metabolites in the brain, conventional methods of magnetic resonance spectroscopy (MRS) yield results that are highly variable and highly dependent on the sequence type being applied. This invention describes a novel MRS technique that involves preparing longitudinal steady states at different flip angles using trains of RF pulses interspersed with field gradients to quantify metabolites.

The molecular imaging technique of positron emission tomography (PET) is an increasingly important tool in biomedical research and in drug discovery and development. Many small molecule drugs and potential PET radiotracers carry trifluoromethyl (CF₃) groups. Because CF₃ groups are generally considered to be metabolically stable, there is a strong interest in developing drugs with these groups.

This technology includes the identification and use of a ketamine metabolite, (2R,6R)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone (HNK), for the treatment of depression. Ketamine is an NMDA receptor antagonist that exerts a rapid and sustained antidepressant and anti-suicidal effect. However, even low doses of ketamine has addictive and psychomimetic effects. The downstream metabolite, (2R,6R)-HNK, does not inhibit the NMDA receptor but recapitulates the antidepressant and anti-suicidal effect of ketamine.