OMX, a novel oxygen carrying protein, for resuscitation in preterm delivery secondary to placental under-perfusion states

Summary: 
While hemoglobin is the primary oxygen delivery molecule used to maintain tissue oxygenation in metazoans, many organisms have other heme-containing proteins that can bind oxygen and other diatomic gases. Here, we tested whether a member of the H-NOX family of heme-containing proteins found in the thermostable bacterium Thermoanaerobacter tengcongensis can be engineered to deliver oxygen to severely hypoxic tissues in large mammals.

Principal Investigators:
Jeffery Fineman, MD | UCSF Department of Pediatrics

Background

While hemoglobin is the primary oxygen delivery molecule used to maintain tissue oxygenation in metazoans, many organisms have other heme-containing proteins that can bind oxygen and other diatomic gases. Here, we tested whether a member of the H-NOX family of heme-containing proteins found in the thermostable bacterium Thermoanaerobacter tengcongensis can be engineered to deliver oxygen to severely hypoxic tissues in large mammals. This class of molecules has the advantage of high oxygen affinity and minimal nitric oxide reactivity.

Objective

Demonstrate that these molecules can effectively deliver oxygen to a lamb heart with induced severe hypoxia, without over-exposing the animal to oxygen or triggering systemic vascular reactivity. These molecules thus represent a novel class of oxygen delivery biotherapeutics to specifically target hypoxic tissue beds without the toxicity concerns of hemoglobin-based oxygen carriers.

Results

As ischemic placental disease processes such as preeclampsia and fetal growth restriction are major drivers of preterm birth, these types of oxygen delivery biotherapeutics may serve as novel therapies to increase oxygen delivery to the growing fetus in this setting. This would have the obvious benefit of supporting fetal well-being and growth, thereby minimizing the need for indicated preterm delivery.