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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).

Parathyroid hormone receptors found on osteoblasts in bone and renal tubule cells in kidney elevate blood calcium levels when stimulated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Excessive secretion of PTH from the parathyroid gland results in primary hyperparathyroidism. Production of PTHrP by various tumors results in humoral hypercalcemia of malignancy. In both of these conditions, excessive blood calcium levels lead to clinically significant morbidity. A parathyroid hormone antagonist could therefore have therapeutic value.

The invention relates to the diagnosis and management of cancer-related fatigue (CRF). More specifically the invention relates to identification and measurement of a single Biomarker or a group of biomarkers (e.g. genes) that are associated with cancer related fatigue. The identification and measurement of such biomarkers can be utilized in the diagnosis and management of fatigue and may facilitate the development of therapy for such fatigue.

The present invention is directed to a transgenic rat model of Alzheimer's Disease (AD) termed TgF344-19+/-. The invention rat overexpresses two human genes (APPswe and PS1deltaE9 genes), each of which are believed to be independent dominant causes of early-onset AD. The hemizygote exhibits major features of AD pathology (i.e., dense and diffuse amyloid plaques, neurofibrillary tangles, cerebral amyloid angiopathy, hyperphosphorylated tau, paired-helical filaments, Hirano bodies, granulovacuolar degeneration, cognitive impairment, and cortical neuronal loss).

Our technology describes unique genetic signatures in patients with digestive diseases and liver disorders. Using comprehensive analysis of 735 microRNAs and 19,000 mRNAs, we have identified a unique set of microRNAs and/or mRNAs which predict disease phenotypes in patients with digestive and liver disorders. The identification of such point-of- care genetic signatures is significant for both personalized biomarkers and novel targeted biotherapeutics. These microRNAs and mRNAs function either together or separately thus modulating protein expressions in one or more signaling pathways.

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 a method for synthesizing the ketamine analogs (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine that may be useful for the treatment of pain, depression, anxiety, and related disorders. The drug ketamine was first used as an anesthetic but was found to be an effective treatment in a range of conditions, including paint, treatment-resistant bipolar depression, and other anxiety-related disorders. However, the routine use of ketamine is hindered by unwanted side effects, including the potential for abuse.

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.