Diagnostic Test and Therapeutic Target for Sjogren's Syndrome

Sjögren's syndrome is an autoimmune disease that attacks salivary glands resulting in chronic dry mouth and dry eyes. Currently, there is no single diagnostic test to confirm the presence of Sjögren's. Physicians presently reach diagnosis after conducting a series of blood and functional tests for tear and salivary production. Diagnosis is further complicated as Sjögren's symptoms frequently mimic those of other autoimmune diseases (e.g., lupus, rheumatoid arthritis, etc.) and is often overlooked as dryness associated with medications being taken by the patient.

mTOR Inhibition for the Prevention of Epithelial Stem Cell Loss and Mucositis

The integrity of the epidermis and mucosal epithelia is highly dependent on self-renewing stem cells and, therefore, is vulnerable to physical and chemical damage from common cancer treatments, such as radiation or chemotherapy. Consequently, many cancer patients undergoing these treatments develop mucositis, a debilitating condition involving painful and deep mucosal ulcerations. Since current prevention and treatment options for mucositis are limited, providing only minor relief and no protection to stem cells, novel therapies are needed.

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).

Role of Novel Hepatitis Delta Virus Variant in Sjogren’s Syndrome

Sjögren’s is a chronic autoimmune disease characterized by dry mouth and eyes, fatigue, and musculoskeletal pain resulting from the attack of the moisture-producing glands by the body’s own white blood cells. The subject invention is based on the discovery of an association between infection by a novel clade 1 variant of hepatitis delta virus (HDV) and primary Sjögren’s syndrome.

Modified AAV5 Vectors for Enhanced Transduction and Reduced Antibody Neutralization

Scientists at the NIH disclosed a mutated adeno-associated virus (AAV) serotype 5 by modifying sialic acid binding regions which mediate viral entry into host cells. Preliminary results from animal studies suggest that this modification can increase transduction by 3-4 folds in salivary glands and muscles, and can significantly decrease the potential of being neutralized by preexisting antibodies compared to the wild type AAV. Thus, the modified AAV5 vectors seem to be optimal for gene therapy.

A Novel Adeno-Associated Virus for Gene Therapy

Scientists at the NIH disclosed a novel adeno-associated virus (AAV) termed "44-9." AAV44-9 based vectors have high gene transfer activity in a number of cell types, including salivary gland cells, liver cells, and different types of neurons (e.g., cells of the cortex, olfactory bulb, and brain stem, and Purkinje cells of the cerebellum). These vectors can increase the transduction efficiency and decrease the potential of being neutralized by preexisting antibodies compared to the wild type AAV.

Rabbit Antisera to Various Matrix, Matricellular, and Other Secreted Proteins

The extracellular matrix (ECM) is composed of a group of proteins that regulate many cellular functions, such as cell shape, adhesion, migration, proliferation, and differentiation. Deregulation of ECM protein production or function contributes to many pathological conditions, including asthma, chronic obstructive pulmonary disease, arthrosclerosis, and cancer. Scientists at the NIH have developed antisera against various ECM components such as proteoglycan, sialoprotein, collagen, etc.. These antisera can be used as research tools to study the biology of extracellular matrix molecules.

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.
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