Oklahoma Medical Research Foundation

University of Kentucky Research Foundation

Hough Ear Institute

Other

University of Oklahoma

Raymond F. Schinazi

Robert a. Floyd

Robert A Floyd

John M Carney

Rheal A Towner

Richard Dana Kopke

Raymond F Schinazi

Robert H Broyles

Kenneth Hensley

Visar Belegu

Dai Nakae

Austin C Roth

Dirk P Dittmer

Yashige Kotake

Rheal Towner

The current invention provides methods and compositions for treating sensorineural hearing loss including but not limited to acute acoustic trauma (AAT). The composition 2,4-disulfonyl &#x3b1;-phenyl tertiary butyl nitrone and N-acetylcysteine (NAC). Preferably, the compositions for treating AAT will be administered orally. However, other methods which deliver the compositions for treating AAT systemically to the body should work equally well.

Methods for treating acute acoustic trauma

The present invention involves the use of 2,4-disulfonyl phenyl tert-butyl nitrone (2,4-ds-PBN) in the treatment and prevention of gliomas. The 2,4-ds-PBN may be used alone or combined with other traditional chemo- and radiotherapies and surgery, to treat or prevent glioma occurrence, recurrence, spread, growth, metastasis, or vascularization.

Adjuvant chemotherapy for anaplastic gliomas

The treatment options for treating blast-induced and noise-induced traumatic brain injury and tinnitus are limited. Thus, the current invention provides methods for treating traumatic brain injury and tinnitus. The methods involve administering a pharmaceutically effective amount of a composition comprising 2,4-disulfonyl &#x3b1;-phenyl tertiary butyl nitrone and N-acetylcysteine (NAC).

Methods for treating brain injury

Methods of treating tinnitus

The treatment options for treating blast-induced and noise-induced traumatic brain injury and tinnitus are limited. Thus, the current invention provides methods for treating traumatic brain injury and tinnitus. The methods involve administering a pharmaceutically effective amount of a composition comprises 2,4-disulfonyl &#x3b1;-phenyl tertiary butyl nitrone and N-acetylcysteine (NAC).

The current invention provides methods and compositions for treating sensorineural hearing loss including but not limited to acute acoustic trauma (AAT). The composition includes compounds which function as free radical traps such as phenyl butyl nitrone (PBN), free radical scavengers, such as edaravone, resveratrol, ebselen and iron chelator and compounds from the family of antioxidant compounds including, but not limited to, N-acetylcysteine (NAC), Acetyl-L-Carnitine (ALCAR), glutathione monoethylester, ebselen, D-methionine and carbamathione. The compositions of the current invention may be delivered by injections or orally.

The invention is a vaccine, and method of vaccination, against RNA viruses, including RNA viruses in the family Flaviviridae, which includes for example West Nile Virus, Yellow fever virus, Dengue fever virus, Hepatitis C virus, Pestiviruses, Bovine viral diarrhea virus, and Classical Swine fever virus, wherein the vaccine comprises the RNA virus or immunogenic portions thereof, which have been treated with and rendered non-pathogenic by a phenothiazine dye and visible light. The invention includes novel strains of WNV for use in producing a vaccine.

RNA virus vaccines and methods

The present invention relates generally to the fields of molecular biology and pharmacology. More particularly, it concerns the use of abscissic acid to treat various diseases, including neurodegenerative diseases and neuromuscular diseases.

Abscissic acid and derivatives thereof for the treatment of diseases

A method is described for regulating gene expression related to iron metabolism to ameliorate diseases that include sickle cell disease, cancers, neurodegenerative diseases, Friedreich's ataxia and other neuromuscular disorders, and atherosclerosis. This approach is illustrated by recent findings that show that ferritin-H, an iron-binding protein that is present in cell nuclei, can repress the human &#x3b2;-globin gene, the gene that is mutated in sickle cell disease. Increased expression of ferritin-H or a related ferritin-family peptide, given to effected cells either as the peptide itself (or a part thereof), as an expression clone of the ferritin-H-subfamily gene, or via a gene regulator that increases expression of the ferritin-H-subfamily gene itself, prevents or ameliorates expression of the disease state in disorders where increased availability of iron is implicated in the etiology of the disease, including those named above.

Gene regulation therapy involving ferritin

PBN (&agr;-phenyl-tert-butylnitrone), and its derivatives nitrone-based free radical traps, significantly reduce preneoplastic nodule development as well as inhibit hepatocellular carcinoma (HCC) formation at very low levels. The involvement of reactive oxygen species (ROS) in cancer development has been strongly implicated for many years. The involvement of ROS has been strongly implicated in cancer development is a model system where feeding a choline deficiency (CD) diet to rats leads to hepatocellular carcinoma (HCC) development. Administering PBN in the drinking water inhibits HCC formation. Preneoplastic nodule growth in the liver is significantly suppressed by administering PBN, or some of its natural metabolites, in the diet. The effectiveness of PBN in preventing HCC development in the CD liver model is considered due to its prevention of tumor development after the target cells have already been initiated, i.e. genetically changed into tumor cells. Administration of PBN (or its potent derivatives) to humans that may already have microscopic tumor preneoplastic nodules should prevent the eventual frank tumor formation.

Nitrone inhibition of cancer development

Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Other preferred spin-trapping agents include 5,5-dimethyl pyrroline N-oxide (DMPO), &agr;-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), and (TEMPO) and spin-trapping derivatives thereof. Examples of derivatives of PBN include halogenated derivatives, bifunctional derivatives, conjugates with drugs or targeting molecules, dimers and cyclodextran polymers of PBN. Many different disorders can be treated using these compounds, including diseases or disorders of the central and peripheral nervous systems, and disorders arising from ischemia, infection, inflammation, oxidation from exposure to radiation or cytotoxic compounds, as well as due to naturally occurring processes such as aging.

Growing community of inventors

Oklahoma City, OK, United States of America

Robert A Floyd