DNA is a foundational biologic molecule and the carrier of genetic information. However, the study of NETs has led to the discovery of the dark side of DNA. DNA released into the extracellular space through the process of NETosis is a key trigger of numerous previously unrecognized pathological functions.
When NET formation overwhelms natural clearance mechanisms, NETs accumulate and trigger a number of pathological mechanisms including autoimmunity, inflammation, fibrosis, thrombosis and tumor metastasis, at the root of many chronic and acute diseases.
DNA is a foundational biologic molecule and the carrier of genetic information. However, the study of NETs has led to the discovery of the dark side of DNA. Extracellular DNA is a key trigger of numerous previously unrecognized pathological functions.
When NETs formation overwhelms natural clearance mechanisms, NETs accumulate and trigger a number of pathological mechanisms including autoimmunity, inflammation, thrombosis and tumor metastasis at the root of several chronic and acute diseases.
Neutrophils are the most abundant immune cells in the human body. They are a critical component of the innate immune system and respond to several stimuli, including immune activation and infectious disease.
When triggered, neutrophils can expel their long chromatin fibers to form NETs. NETs are an ancient part of the innate immune system and are believed to have evolved as an antibacterial defense mechanism to create a “bio-bandage” around wounds. In humans, NETs deployed in the wrong place for too long are a root cause of several major diseases.
Once released, NETs act as molecular magnets for autoantibodies and other inflammatory proteins. Their extended DNA and histone scaffold presents a dense, multivalent array of nucleosomes, creating thousands of potential binding sites for anti-DNA autoantibodies. This enables a single NET to capture and concentrate large numbers of autoantibodies, complement proteins, cytokines, profibrotic mediators, and coagulation factors into stable macromolecular complexes. The resulting immune complexes amplify inflammation, tissue injury, and immunothrombosis, contributing to disease flares in conditions such as lupus.
The exDNASE™ platform powers the design, rapid prototyping and manufacturing of DNASE enzyme analogs of naturally occurring enzymes. Molecules produced by the platform are designed with an enhanced ability to disassemble NETs and optimized for therapeutic properties. Previous NETs treatment strategies have predominantly focused on inhibiting NETs formation and have not led to clinically effective anti-NET treatments.
Upon administration of Neutrolis’ therapies, NETs are immediately disassembled into nucleosomes to attenuate their pathological function.
Once NETs are disassembled into nucleosomes, there is a million-fold reduction in the size of the NET complex, and flare-triggering properties are eliminated. The nucleosome byproducts are of uniform length and become soluble in blood, which makes them helpful pharmacodynamic markers to guide the development and administration of Neutrolis' therapies.
Our proprietary exDNASE™ platform is based on the naturally selected enzymes that evolved to disassemble the extracellular chromatin that forms NETs. The platform powers the design, rapid prototyping, selection and manufacturing of engineered enzyme analogs with enhanced ability to disassemble NETs and optimized for use in different therapeutic settings. Neutrolis' lead program, NTR-1011, is being initially developed to address systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
A decriptive sentence should go here to give context to the infographic below.
Neutrolis, Inc.
1 Broadway
Cambridge, MA 02142
