This technology includes the identification and use of a combination therapy consisting of human recombinant N-acetylgalactosamine-6-sulfate sulfatase (hrGALNS) and the pharmacological chaperone compounds Ezetimibe and Pranlukast for the treatment of Mucopolysaccharidosis Type IVA (MPS IVA). MPS IVA is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Currently, hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are available for patients with MPS IVA.

The current invention provides nucleic acid sequences comprising the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 1b. It covers the use of these sequences, and polypeptides encoded by all or part of the sequences, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.

This technology includes the use of the small molecule metarrestin (ML246) for the treatment of several types of pancreatic cancer. A subcellular structure called the perinucleolar compartment (PNC) is frequently found in metastatic tumors and cancer stem cells. Reduction of PNC prevalence followed by medicinal chemistry was used to identify metarrestin as a compound that reduces PNC prevalence without significantly impacting cell viability. In vitro and in vivo animal work have demonstrated desirable pharmacokinetic properties as well as a reduction in metastatic burden and extended survival.

Local inflammation processes are crucially important in the host defense against pathogens and for successful immunization because proinflammatory cytokines are necessary for initiation and propagation of an immune response. However, normal inflammatory responses are eventually terminated by physiological termination mechanisms, thereby limiting the strength and duration of immune responses, especially to weak antigens. The inventors have shown that adenosine A2a and A3a receptors play a critical role in down-regulation of inflammation in vivo.

The invention provides identification methods for agents which inhibit the Jak-STAT signaling transduction pathway. Drugs identified by these methods are candidates for the treatment of proliferative disorders dependent on the Jak-STAT pathway, including those caused by HTLV-1. In addition, such agents may be potent immunosuppressive drugs with potential applications not only for organ transplantation but also for treatment of autoimmune diseases.

ADP-ribosylation of arginine residues in proteins may be involved in cell adhesion and is crucial for the action of cholera toxin and E. coli heat-labile enterotoxin, agents involved in the pathogenesis of cholera and traveller's diarrhoea, respectively. ADP-ribosylation is reversed by ADP-ribosylarginine hydrolases, which cleave the ADP-ribose-arginine bond. ADP-ribosylarginine hydrolases from a variety of mammalian species and tissues were isolated, and the coding regions for the hydrolases were cloned and expressed.

The invention described and claimed in these patent applications provides for novel hybrid vectors which may be used for cell transformation either in vivo, in vitro, or ex vivo. The hybrid vectors, which are capable of integrating into the chromosome of the host cell and are capable of transducing dividing and non-dividing cells, have an adenoviral serotype 5 backbone and two retroviral (Moloney murine leukemia virus) elements upstream and downstream of the transgene.

Cell transplantation therapy typically involves transplanting primary cells or immortalized cells into patients. The promising but still inconsistent data stemming from those clinical trials using primary cells in Parkinson's disease are believed to be due to an insufficient number, function and uniformity of the transplanted cells. In an effort to overcome these problems an improved method for isolating, growing and differentiating precursor cells into dopaminergic neurons has been developed.

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.

Hearing loss is a common communication disorder affecting nearly 1 in 1,000 children in the United States alone, and nearly 50% of adults by the age of eighty. Hearing loss can be caused by environmental and disease-related factors; however, hearing loss due to genetic factors accounts for approximately 50% of cases.