Locally Delivered Alkaline Phosphatase for Treatment of Periodontal Disease

This technology includes a product for local delivery of alkaline phosphatase for the treatment of periodontal disease. Our laboratory has discovered that factors regulating phosphate metabolism and specifically the appropriate balance between phosphate (Pi) and pyrophosphate (PPi) at local sites are needed for formation (development), maintenance and regeneration of the tooth root surface (cementum), periodontal ligament (PDL) and surrounding alveolar bone, i.e., the periodontal apparatus.

Development of Immune System Tolerance for the Treatment of Autoimmune Disease

The present invention provides a therapeutic method for the treatment of autoimmune or autoinflammatory diseases by first breaking down the dysregulated immune system and then reprogramming the immune system to restore tolerance to the patient's self-antigens by induction of antigen specific regulatory T cells. The inventors have shown that only with the combination of apoptosis, phagocytes, and antigen can antigen-specific regulatory T cells (Treg) cells be optimally generated to develop long-term immune tolerance.

Methods of Treating or Preventing Pruritis (Itch)

This technology provides a novel method of treating or preventing pruritis (itch) using natriuretic polypeptide b (Nppb) blocking agents. Itch (also known as pruritis) is a sensation that may be perceived as an unpleasant skin irritation and may drive an urge to scratch. Conditions such as, for example, psoriasis, atopic dermatitis, renal failure, liver cirrhosis and some cancers may cause persistent itch. Itch is triggered by somatosensory neurons expressing the ion channel TRPV1 (transient receptor potential cation channel subfamily V member 1).

mNFHcre Transgenic Mice

Knockout mouse is a valuable model to study biological functions of target genes. When Cre expressing mice are bred with mice containing a loxP-flanked gene, the gene between the loxP sites will be deleted in the offsprings. Scientists at the NIH have generated mNF-H-cre transgenic mouse lines that express Cre recombinase under the control of the promoter of the neurofilament-H gene, which is expressed in the late stage of neuronal maturation. The transgenic mice express cre in neurons (but not astrocytes) with highest expression in the cortex and hippocampus.

Potential New Drugs for Treating or Preventing Pruritus

NIH scientists have identified new compositions that could potentially be used to treat or prevent pruritus (itchiness). The newly discovered compounds can block a newly identified itch pathway and might be effective for persistent itch caused by psoriasis, atopic dermatitis, renal failure, liver cirrhosis and chemotherapy. These compounds are different from commonly used antihistamines which induce drowsiness and sedation. These compounds have the potential to be used for human and animals.

KCNN4 Knockout Mice for Mechanistic Research

This technology includes a transgenic allele for a mouse knockout model for the KCNN4 gene. Secretion of fluids from these salivary glands requires the coordination of multiple water and ion channel proteins. Notably, the majority of these channels have been shown to be up-regulated by increased calcium concentrations. The relevant calcium-activated potassium channels are split into the small, intermediate, and large conductance channels (called the SK, IK, and BK channels). The KCNN4 gene plays a part in the IK and BK channels.

Treating Kidney Disorders and Diabetic Nephropathy with N-acetyl mannosamine (ManNAc)

N-acetylmannosamine (ManNAc) is a small uncharged physiological molecule that crosses membranes readily and is the natural precursor of intracellular sialic acid synthesis. NHGRI investigators discovered that ManNAc can be used for therapeutic purposes, including treating certain kidney diseases (e.g., those involving proteinuria and hematuria), resulting primarily or secondarily from hyposialylation (lack of sialic acid). Notably, ManNAc can also be used to treat diabetic nephropathy or diabetes.

Treatment of Periodontal Disease via ENPPI Inhibition

This technology focuses on enhancing cementum production, a key component in treating periodontal regression. The method involves inhibiting ectonucleotide pyrophosphatase phosphodiesterases (ENPP1), enzymes that play a significant role in mineralization processes. Pyrophosphate (PPi) is known to impede the growth of hydroxyapatite crystals, essential for mineralization. ENPP1 catalyzes the hydrolysis of ATP, generating PPi, which then hinders mineralization.

Deuterated alpha5 Subunit-selective Negative Allosteric Modulators of Gamma-Aminobutyric Acid Type A Receptors as Fast Acting Treatments for Depression and Mood Disorders

This technology includes GABAa a5 Negative Allosteric modulators (GABAa a5 NAMs) which have been recently discovered to act as fast-acting antidepressants in a variety of mouse models of depression. These NAMs are actively metabolized in vivo. This invention involves the conceptualization and synthesis of GABAa a5 NAM molecules with a deuterium in the active metabolic position. This significantly increased the metabolic stability, while still retaining the antidepressant activity.
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