"Unlike hemoglobin-based oxygen carriers, OMX-CV is fine-tuned to only release oxygen under pathologic conditions," said Ana Krtolica, PhD, vice president of research at Omniox and co-senior author of the paper. The researchers also showed that the modified proteins bind oxygen so tightly that they only relinquish their grip when they come across a severely hypoxic tissue.
By modifying the chemical structure of H-NOX proteins, Omniox scientists reengineered them to hold tight to oxygen, but leave nitric oxide alone.
H-NOX proteins contain a "co-factor" called a heme group - the same co-factor that gives hemoglobin its name - which allows the protein to bind not only oxygen but also nitric oxide. OMX-CV sidesteps these problems by employing an engineered bacterial protein known as H-NOX as its base, rather than hemoglobin. Vessels robbed of nitric oxide constrict, causing blood pressure to jump, raising the risk of heart attack and decreasing blood flow to important organs like the kidneys. Moreover, when outside the bounds of a red blood cell, hemoglobin can grab hold of nitric oxide, a natural muscle relaxant found in blood vessels. Hemoglobin-based drugs have proven too good at their jobs: they tend to flood the blood with excess oxygen that can itself cause serious tissue damage. But these treatments also carry a lot of baggage. Scientists have tried to design ways to fight hypoxia by delivering oxygen on the back of hemoglobin, the protein that lets red blood cells shuttle oxygen throughout the body and also produces their scarlet color. An oxygen-delivering drug like OMX-CV could ease the physical stress of hypoxia and improve recovery following heart attacks or after open heart surgery in adults and children. The hypoxic heart pumps harder to deliver oxygen to the rest of the body, and paradoxically, requires more and more oxygen itself to maintain function. Under normal conditions, the heart consumes more oxygen by weight than any other organ, and when oxygen levels are low, its demand soars even higher. Many of these infants require heart surgery within their first year of life, during which blood may be temporarily removed from the heart, leaving the organ starved for oxygen. According to the Centers for Disease Control and Prevention (CDC), about 10,000 children are born each year with a critical congenital heart defect. Hypoxia During Heart Disease - an Unmet Clinical ThreatĬardiovascular diseases such as coronary artery disease can starve the heart of oxygen, triggering cardiac dysfunction or heart attacks in adults, but hypoxia in the heart is also a problem in children.
Omniox, which was among the first startup biotech companies to launch in the QB3 "Garage" incubator space on UCSF's Mission Bay campus, in 2010, teamed up with Maltepe and other UCSF researchers to test the treatment, and published their findings October 18, 2018, in the journal PLOS Biology. a biopharmaceutical company developing oxygen-delivery therapeutics for the treatment of cancer, cardiovascular diseases, trauma and other conditions in which low oxygen levels, or hypoxia, negatively impact disease outcomes. The new drug, called OMX-CV, was developed by Omniox, Inc. "Any tissue with compromised blood flow, whether due to trauma, stroke, or heart disease, could potentially be targeted by a treatment like this," said Emin Maltepe, MD, PhD, associate professor of pediatrics at UCSF and co-senior author of the paper. Instead, the new drug delivers its precious oxygen cargo only to the tissues that need it most. Unlike its experimental predecessors, the new drug does not appear to cause systemic side effects or overcorrect with excessive blood oxygenation, which can itself be toxic. In new studies conducted at UC San Francisco, a novel oxygen-delivery therapeutic restored the function of oxygen-starved heart tissue in an animal model of global hypoxia.
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