Nanoparticles Could Help Alleviate a Rare Respiratory Disorder Among Newborns

A new therapy based on nanoparticles can help against a rare and complex disease that usually ends up fatal for newborns.

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a very rare congenital disorder that causes severe and often fatal respiratory problems and high blood pressure in the blood vessels of the lungs, according to the National Organization for Rare Disorders (NORD). While there are only about 200 documented cases of ACDMPV worldwide, there remains an unknown number of infants who might have died prematurely without even being diagnosed with the condition.

The disease is believed to be caused by genetic abnormalities that lead to improper formation of blood vessels in the lungs. From a few days to several weeks after birth, newborns suddenly turn blue from lack of oxygen while the lungs begin registering higher-than-normal blood pressure levels. Even rarer survivors of the conditions managed to do so by receiving lung transplants, which are extremely rare because of their infant size.

Delivery of Nanoparticles Against ACDMPV

The new study using nanoparticles was led by experts at Cincinnati Children's Hospital Medical Center and the University of Cincinnati. In the article "Nanoparticle Delivery of STAT3 Alleviates Pulmonary Hypertension in a Mouse Model of Alveolar Capillary Dysplasia," published June 11 in the journal Circulation, researchers report helping mice with a FOXF1 mutation, which gives them a condition similar to human patients with ACDMPV. Mice who received the nanoparticles as a part of the treatment method survive longer, with these advanced nanoparticles delivering a form of the STAT3 gene into the lungs, stimulating blood vessel growth.

STAT3, a member of the signal transducer and activator of a transcription protein family, is also a key downstream target of FOXF1, and the delivery of the gene could correct the vascular deficiency in ACDMPV mice.

Authors of the study say that if the same results could be replicated in human studies in the future, this could spur the development of other therapies that use nanoparticles to treat a wide variety of conditions.

"Nanoparticle carriers have shown minimal toxicity and have accelerated the development of novel therapies for human cancers, diabetes and chronic inflammatory disorders. We have developed a unique nanoparticle delivery system that can deliver genes capable of stimulating micro-vessel growth in the newborn lung," says Vlad Kalinichenko, MD, Ph.D., the senior author of the study and a member of the Perinatal Institute at Cincinnati Children's as well as the Center for Lung Regenerative Medicine, in a statement from the Children's Hospital.

Without the treatment with the nanoparticles, about 70 percent of the ACDMPV mice die within 28 days from birth. The new therapy cuts the mortality rate down to 35 percent.

Gene-Driven, Not Gene Editing

Researchers clarify that the new treatment with nanoparticles is not like gene editing or gene replacement methods that create permanent changes to the patients' bodies. The new gene-driven treatment does not last in the body for more than seven days. However, the period was enough to prevent a host of problems that would've developed later on with ACDMPV patients.

The new therapy works through the targeted delivery of nanoparticles made up of polymers, fatty acids, and a cholesterol component that carries the non-integrating STAT3 protein, encouraging blood vessel growth around the lungs.

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