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Atopic dermatitis (AD) is a common, recurrent, chronic inflammatory skin disease that is a cause of considerable economic and social burden. It is one of the most prevalent skin disorders, affecting ~25% of children in developed and developing countries and is expected to continue to escalate. This increased rate of incidence has changed the focus of research on AD toward epidemiology, prevention, and treatment.

Rabies virus (RABV) infection leads to fatal encephalitis—inflammation of the brain—if left untreated. Millions of people survive RABV infection each year due to timely administration of post-exposure treatment, however, nearly 60,000 people die from rabies each year according to the World Health Organization. Obstacles to timely treatment for RABV infection include the high cost and burdensome storage requirements (i.e., refrigeration) of current post-exposure treatments (i.e., rabies immunoglobulin (RIG)).

The ongoing COVID-19 pandemic, caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an immense public health, social, and economic burden. Variants of concern continue to emerge that have increased transmissibility, pathogenicity, or both and that reduce the effectiveness of current therapeutics and vaccines. Thus, there is a great need for broadly protective therapeutics.

Scientists at NCATS have developed a novel Cellular Thermal Shift Assay (CETSA), named “Real-time CETSA” in which temperature-induced aggregation of proteins can be monitored in cells in real time across a range of compound concentrations and simultaneously across a temperature gradient in a high-throughput manner. Real-time CETSA streamlines the thermal shift assay and allows investigators to capture full aggregation profiles for every sample.

Scientists at NCATS have developed an analog of Methotrexate (MTX) that incorporates the proteasome-targeting properties of E3-ubiquitin ligase small molecule ligands (MTX-PROTACs) to directly bind to the MTX target dihydrofolate reductase (DHFR) and mark the protein for proteasomal degradation. This unique property may dramatically lower the therapeutic dose required in a treatment setting.

The invention includes compounds and compositions for inhibiting phosphoglycerate mutase (PGM) activity. In some examples, the compounds selectively inhibit cofactor-independent PGM (iPGM). In particular embodiments, the compounds include one or more cyclic peptides.

Interferons (IFNs) are a family of cytokines that function in response to an immune challenge such as a viral or bacterial infection. Type I IFNs are produced by immune cells (predominantly monocytes and dendritic cells) as well as fibroblasts and signal through a specific cell surface receptor complex (IFNAR) that consist of IFNAR1 and IFNAR2 chains. Type-I IFNs exert several common effects including antiviral, antiproliferative, and immunomodulatory activities. However, Type I IFNs also have pro-inflammatory effects, especially in the presence of TNF-a.

Malaria continues to be a life-threatening disease, causing roughly 241 million cases and an estimated 627,000 deaths in 2020, mostly among African children, although in 2020 nearly half of the world’s population was at risk of malaria. There is a big financial burden for antimalarial treatment; direct costs (for example, illness, treatment, premature death) have been estimated to be at least US $12 billion per year and the cost in lost economic growth is many times more than that.

In the last decade, prescription opioid abuse and misuse has been a major contributor to mortality in the United States, resulting in a serious national public health crisis. Nearly 12 million Americans used prescription opioids nonmedically in 2018, with >67,000 people dying from an opioid overdose.

The technology encompasses antibodies and methods that may overcome the shortcomings of commercial checkpoint inhibitors (CPIs). Scientists at NIAID have identified MHC-I specific antibodies that selectively inhibit interactions with inhibitory leukocyte immunoglobin-like receptors (LILRs) but not T-cell receptors. Administration of the antibodies increased proliferation and activation of both innate and adaptive immune system cells, and lead to anti-tumor and anti-viral activity in an array of relevant mouse models of disease.