RSV is the most important viral agent of severe respiratory disease in infants and young children worldwide and also causes substantial morbidity and mortality in older adults. RSV is estimated to cause more than 33 million lower respiratory tract illnesses, three million hospitalizations, and nearly 200,000 childhood deaths worldwide annually, with many deaths occurring in developing countries. However, despite the prevalence of RSV and the dangers associated with infection, no RSV vaccine has been successfully developed to date.

Allergic reactions affect nearly 40 million persons in the United States. Allergic reactions are due to a sequential interaction beginning with the extracellular aggregation of the high affinity receptor for IgE (FcepsilonRI) followed by intracellular tyrosine phosphorylation which initiates a further cascade of events eventually leading to histamine and cytokine release. The reaction is initiated by Lyn kinase which is pre-associated with the FcepsilonRI.

This technology includes the development and use of small molecule activators of pyruvate kinase (PK) for the treatment of inherited nonspherocytic hemolytic anemia, including PK deficiency. PK deficiency is caused by an inherited deficiency in an enzyme that reduces the lifespan of red blood cells. More than 150 unique mutations have been identified in the PK gene that lead to decreased activity in this essential enzyme in the glycolytic pathway. The prematurely lysed red blood cells can lead to jaundice, splenomegaly, and a hemolytic anemia.

This technology includes the identification and use of niclosamide analogs and prodrugs for the treatment of SARS-CoV-2 infection. In-vitro studies have found niclosamide, an old anthelminthic drug, to be potent and effective against Covid-19. But the broad antiviral effect of niclosamide is offset by the low solubility of the drug, leading to poor oral absorption. The niclosamide analogs and prodrugs included in this technology have better in vitro physicochemical properties. Also, these analogs were comparable to niclosamide in the in-vitro 3D models of SARS-CoV-2 infection.

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.

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.

Homocystinuria (HCU), a group of inherited disorders, causes symptoms ranging from failure to thrive and developmental delays in infants or young children to abnormal blood clots with onset in adults.1 Approximately 1 in 200,000 to 335,000 people have HCU globally.2

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.

Nestin is an intermediate filament protein first described in early embryonic neuroepithelial stem cells. Although not found in most cells of the mature CNS, nestin is the predominant marker used to detect the small population of undifferentiated cells. The presence of nestin identifies stem, progenitor and some tumor cells in the CNS, and also labels areas of reactive gliosis in the CNS. Available methods to detect nestin use antibodies generated against rat nestin protein.

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.