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NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.

This invention discloses small molecule inhibitors of human 12-lipoxygenase (12-hLO). 12-lipoxygenase expression, activation, and lipid metabolites have been implicated in type 1 and type 2 diabetes, cardiovascular disease, hypertension, Alzheimer’s, and Parkinson’s disease. The development of 12-hLO inhibitors may be a potent intracellular approach to decreasing the ability of platelets to form large clots in response to vessel injury or activation of the coagulation pathway.

This invention discloses methods for treating neurodegenerative diseases by administering cyclin dependent kinase 5 (Cdk5) inhibitory peptides derived from P35, the activator of Cdk5. Abnormally hyperactive Cdk5 has been shown to be associated with a variety of neurodegenerative disorders. Disclosed in this invention are isolated peptide fragments, pharmaceutical compositions and methods for use of such for treating subjects with a neurodegenerative disease, such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD).

NIH Inventors have recently discovered a novel Leucine-rich repeat and calponin homology domain-containing protein 4 (Lrch4) in a proteomic screen of the plasma membrane of lipopolysaccharide (LPS)-exposed macrophages. Expression data by RT-PCR revealed that all Lrch family members (1-4) are expressed in macrophages, but only Lrch4 was recruited into lipid rafts (signaling microdomains of the plasma membrane) by LPS. Lrch4 is the most highly expressed Lrch family member in mouse tissues. It is a predicted single-spanning transmembrane protein that is encoded by the Lrch4 gene in humans.

Cerebral Cavernous Malformation (CCM) is a brain disease affecting up to 0.5% of the worldwide population. CCM is characterized by grossly dilated vessels prone to leaking and hemorrhage which result in severe headaches, seizures, and strokes. Inherited forms of the disease are due to mutations in one of three loci, CCM1, CCM2, and CCM3. Prior efforts to develop mice with targeted null mutations in Ccm1, Ccm2, or Ccm3 have been unsuccessful, as such mutations result in embryonic death.

This technology is a collection of small molecules screened for their ability to prevent or reduce the cytotoxic effects of the protein, Huntingtin. Huntington's disease is a neurodegenerative disorder due to a dominantly acting expansion of a CAG trinucleotide repeat in exon 1 of the Huntington (HTT) gene resulting in production of the altered (mutant) protein Huntingtin, which has a long chain of polyglutamine (poly Q) attached to the exon 1 encoded protein sequence.

The retinoid-related orphan receptors alpha, beta and gamma (RORalpha, beta and gamma , also referred to as NR1F1, 2 and 3, respectively) comprise a distinct subfamily of nuclear receptors. Study of ROR-deficient mice has implicated RORs in the regulation of a number of biological processes and revealed potential roles for these proteins in several pathologies. NIH investigators have developed an in-vitro system using CHO cells stably expressing a TET-On expression vector regulating RORgamma and a RORE-Luciferase reporter.

Early work by Hammond at al. showed gamma globulin to be effective for the prevention of poliomyelitis. Therefore, passive immunotherapy could be another way to treat chronic excretors. Even though prior attempts to use intravenous immunoglobulin (IVIG) and breast milk were unsuccessful, there is reason to think that higher doses of antipoliovirus antibodies could result in complete clearance of poliovirus from chronically infected individuals.

TBEV causes serious illnesses from meningitis to meningo-encephalitis, totaling 3,000 cases of hospitalization in Europe and between 5,000-10,000 cases in Russia reported every year. The Far Eastern hemorrhagic TBEV strains are associated with a mortality rate (between 1-2%), higher than other strains isolated in the Siberia or Western Europe. There is a high proportion (up to 46%) of TBEV patients with temporary or permanent neurological sequelae.

Species of Bacillus, such as Bacillus anthracis, Bacillus cereus, and Bacillus subtilis, are attractive microorganisms for recombinant protein production in view of their fast growth rate, high yield, and ability to secrete produced products directly into the medium. Bacillus anthracis is also attractive in view of its ability to produce anthrax toxin and ability to fold proteins correctly. This application claims a B. anthracis strain in which more than one secreted protease is inactivated by genetic modification.