John W. Chen, MD, PhD | Massachusetts General Hospital and Harvard Medical School; Cuihua Wang, PhD | Massachusetts General Hospital and Harvard Medical School
Competition Sponsor: US National Academy of Medicine
Awardee Year: 2022
Oxidative stress is postulated to be involved in aging and many diseases. When oxidative species are elevated and overwhelm the antioxidant balance excess oxidants can contribute to aging and disease. However, no currently available method can sensitively and specifically pinpoint the locations/organs where aberrant oxidant production is occurring, critically hampering oxidative stress research and clinical application of antioxidant therapeutics. Thus, there is an unmet need for a marker of excess oxidant production to better understand the role oxidative stress plays in aging and disease. We have accidentally discovered an undescribed relationship between myeloperoxidase (MPO) and normal aging. MPO is a key enzyme involved in generating oxidative stress and produces highly reactive oxygen and nitrogen species that cause protein aggregation, cell signaling interruption, mutagenesis, and tissue damage. We also recently described a positron emission tomography (PET) imaging probe that can specifically and sensitively detect MPO activity, and verified that this probe can cross the blood-brain barrier. We propose to use this imaging probe to track non-invasively MPO activity in the brain over time in normal aging in mice. We hypothesize that this imaging technology can spur antioxidant research and enable personalized treatment plans to improve health and longevity and prevent aging and age-related diseases. Because PET imaging agents are administered at a microdose level, the cost for translation is significantly lower than for other types of drugs. Thus, we anticipate that once validated in animal models, this technology can be quickly translated and applied to study human aging.
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