Scientist/Adjunct Associate Professor Vasculotox NY, New York, United States
Abstract: VasculoTox is developing tools to enable clinical selection and development of appropriate immunomodulator treatment to achieve remission (or delay progression) in chronic and acute inflammatory disorders affecting the brain. Our goal is to provide an FDA approved theranostic strategy that will achieve remission and prevent/delay neurodegenerative disease (ND) progression by reducing neuroinflammation and vascular dysfunction. Technology Differentiator. Specific to tumor necrosis factor (TNF)-mediated disease models (such as Rheumatoid Arthritis [RA]), our preliminary results support a robust theranostic approach to achieving remission and preventing/delaying ND development based on assessment of neuroinflammation acting as a driver for neurovascular dysfunction. Rigor of Prior Research. Neuroinflammation driven by TNF is a presymptomatic hallmark of major ND, including Parkinson's Disease (PD), Alzheimer's Disease (AD), and Multiple Sclerosis (MS). Anti-inflammatory drugs have been shown to be protective against ND in patients with RA; however, the level of protection associated with different anti-inflammatory drugs varies and may be driven by patient-specific factors. A study of 8.5 million (M) commercially-insured adults in the United States, Puerto Rico, and U.S. Virgin Islands demonstrated that patients with RA taking the TNF inhibitor Etanercept had a reduced risk of AD, including cognitive deficits and dementia, compared to those taking other TNF inhibitors or non-specific anti-inflammatories such as methotrexate (MTX). Etanercept inhibits both TNF-alpha (TNFα) and Lymphotoxin Alpha (also referred to as LTα/TNF-beta [protein]; LTA/TNFB [gene]), while other TNF inhibitors do not have this dual activity. Preliminary data. We have gathered significant preliminary evidence that links a gain-of-function (GoF) single nucleotide variant (SNV) of LTA/TNFB, thereby extending the Etanercept paradigm. Impact and value of the technology. The direct and indirect cost of PD alone is estimated to be nearly $25 billion per year in the U.S., with AD being even more costly. Significant NIH and venture funding are being directed towards disease-modifying therapies and regenerative medicine. In this and other therapeutic contexts, theranostic siRNAs are critical for target selection and early assessment of efficacy, standing in contrast to the established acute treat-to-target (T2T) strategy that is widely used. Impact of innovation on state of the science/technology. These ClinicoPathological Correlation (CPC) ImmunoTechnologies, which will include siRNAs and cellular screening assays, are part of a long-game, synergistic, precision medicine strategy to provide superior neuroinflammation control.
