SIRT2 Inhibitors as Novel Therapeutics for Myocardial Infarction and Ischemic Stroke and to Prevent Necrosis

Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice.

Vitamin D Receptor Antagonists for Treating Breast Cancer

Vitamin D receptor (VDR) is a nuclear receptor that is activated by calcitriol, the active form of vitamin D. It is best known for regulating dietary calcium uptake necessary for bone growth, but it also affects cell proliferation and differentiation. Therefore, it was thought that treatment with calcitriol or its derivatives could be useful to treat the uncontrolled proliferation typical of cancer cells. However, this approach has been unsuccessful to date because it leads to toxic levels of calcium in the blood.

A Mouse Model for Systemic Inflammation in Glucocerebrosidase-Deficient Mice with Minimal Glucosylceramide Storage

Gaucher disease, the most common lysosomal storage disease, is an inherited metabolic disorder in which harmful quantities of the lipid glucocerebroside accumulate in the spleen, liver, lungs, bone marrow and in rare cases in the brain, due to a deficiency of the enzyme glucocerebrosidase (Gba) that catalyses the first step in the biodegradation of glucocerebrosides. Type 1 Gaucher disease is the most common and is distinguished from the other forms of the disease, types 2 and 3, by the lack of neurologic involvement.

Rapid and Sensitive Detection of Nucleic Acid Sequence Variations

The ability to easily detect small mutations in nucleic acids, such as single base substitutions, can provide a powerful tool for use in cancer detection, perinatal screens for inherited diseases, and analysis of genetic polymorphisms such as genetic mapping or for identification purposes. Current approaches make use of the mismatch that occurs between complimentary strands of DNA when there is a genetic mutation, the electrophoretic mobility differences caused by small sequence changes, and chemicals or enzymes that can cleave heteroduplex sites.

Generation of Smad3-null Mice and Smad4-conditional Mice

SMADs are a novel set of mammalian proteins that act downstream of TGF-beta family ligands. These proteins can be categorized into three distinct functional sets, receptor-activated SMADs (SMADs 1,2,3,5, and 8), the common mediator SMAD (SMAD 4), and inhibitory SMADs (SMADs 6 and 7). SMAD proteins are thought to play a role in vertebrate development and tumorigenesis.

A Broadly Protective Human Antibody for GI Genogroup Noroviruses

Norovirus is a leading cause of vomiting, diarrhea, and foodborne illness worldwide, with 700 million cases and 200,000 deaths occurring each year. Despite decades of work in the field, there are no preventive or therapeutic strategies specifically approved for even the most prevalent forms of human norovirus (i.e., GI, GII genogroups), which are highly contagious and carry an increased risk of severe complications in children, older adults, and those with immunocompromising conditions. 

A Novel Strategy to Produce 6-cys Proteins Based on Pfs230D1 Domain Fusions

The Plasmodium parasite has a complex lifecycle during human infection and in the mosquito vector. Most advanced malaria vaccine candidates can confer only partial, short-term protection in malaria-endemic areas. A means of breaking the transmission of malaria to subsequent individuals could prevent a significant amount of human disease.

The primary embodiments of this technology are novel compositions of matter that produce enhanced transmission-blocking responses over current transmission blocking vaccines:

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