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Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and is also a frequent cause of bloodstream, brain and spinal cord, ear, and sinus infections. According to 2015 CDC data, an estimated 900,000 Americans get pneumococcal pneumonia each year and approximately 5-7% die from it annually. Accurate diagnosis and early treatment are important for improving patient outcomes.

This technology is directed towards a potential treatment for a new disease, CHAPLE (Complement Hyperactivation, Angiopathic thrombosis, and Protein-Losing Enteropathy), identified by NIAID researchers. CHAPLE is associated with GI symptoms and vascular thrombosis and is caused by loss-of-function variants in the gene encoding the complement regulatory protein CD55. The disease is caused by enhanced activation of the complement pathway and complement-mediated induction of intestinal lymphangiectasia and protein-losing enteropathy.

The technology addresses treatment options for diseases such as sickle-cell and thalassemia. Traditionally, such beta-globinopathies are treated through bone marrow transplantation. However, this method is limited due to high treatment costs and finding a matched-donor. This relies on increasing fetal hemoglobin to potentially cure the disease. NIH inventors have identified a protein called Rio-Kinase 3 (RIOK3), that inhibits the production of fetal hemoglobin. Their work shows that inhibiting RIOK3 increases the production of fetal hemoglobin.

Clinical and biological specimens often contain microbial nucleic acid in extremely low quantities, presenting a significant challenge for the detection of viral and bacterial pathogens. This also prevents direct sequencing of non-culturable samples using next-generation sequencing (NGS). Currently, NGS library preparation on most platforms requires 0.1 ng to 10 µg of DNA or cDNA, while microbial or viral nucleic acids in clinically relevant specimens, such as blood, serum, respiratory secretions, cerebral spinal fluid, and stool, often contain less than 0.1 ng.

The technology describes the composition of small molecule compounds that are antagonists of the P2Y14 receptor. Also provided are methods of using the compounds, including a method of treating a disorder, such as inflammation, diabetes, insulin resistance, hyperglycemia, a lipid disorder, obesity, a condition associated with metabolic syndrome, and asthma, and a method of antagonizing P2Y14 receptor activity in a cell.

The technology discloses composition of compounds that fully antagonize the human P2Y14 receptor, with moderate affinity with insignificant antagonism of other P2Y receptors. Therefore, they are highly selective P2Y14 receptor antagonists. Even though there is no P2Y14 receptor modulators in clinical use currently, selective P2Y14 receptor antagonists are sought as potential therapeutic treatments for asthma, cystic fibrosis, inflammation and possibly diabetes and neurodegeneration.

During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

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 lentivirus vectors to be used to treat sickle cell disease and beta thalassemia. (i) Lin28A or Lin28B vectors designed for erythroid-specific expression using EKLF1, SPTA1, or similar erythroid-specific regulatory elements will be used to transduce hematopoietic stem cells isolated from humans with sickle cell disease or beta-thalassemia syndromes.

Congenital hydrocephalus is a significant public health problem, affecting approximately one in 500 live births in the United States. Congenital hydrocephalus has an adverse effect on developing brain and may persist as neurological defects in children and adults. Some of these defects may manifest as mental retardation, cerebral palsy, epilepsy and visual disabilities. Improved diagnostics are needed for assessing the risks of developing this debilitating disease.