Respiratory Care Currents

 Published: June 29, 2021

By: Debbie Bunch

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Promising New Therapy for CF

In a study, supported in part by the National Institutes of Health and the Cystic Fibrosis Foundation, researchers led by a group from the University of North Carolina School of Medicine have uncovered a new strategy for treating people with cystic fibrosis.  

The strategy involves a novel method to deliver small nucleic acid molecules called oligonucleotides, which can correct some of the defects involved in CF, into the cells of the lungs. While the FDA has approved two splicing therapies to get these molecules into the appropriate cells for people with inherited muscular disorders, those therapies don’t work well for the lungs. In this study, the investigators added two new features to the therapy to overcome those obstacles.  

First, the oligonucleotides were connected to short, protein-like molecules called peptides designed to help them distribute in the body and get into cells. Second, a separate treatment with small molecules helped the therapeutic oligonucleotides escape their entrapment within endosomes, which typically happens after entering the cells, allowing them to reach their target. 

They tested the combined approach in cultured airway cells from a human CF patient with a common splicing-defect mutation. “Adding it just once to these cells, at a relatively low concentration, essentially corrected CFTR to a normal level of functioning, with no evidence of toxicity to the cells,” said senior study author Silvia Kreda, PhD. 

More preclinical studies are being planned to further investigate the potential of this new treatment for CF. 

The study was published in Nucleic Acids Research in June.  

Stiffening Airways May Contribute to Asthma Attacks

Northeastern University researchers believe they have found a new target for treatments to ease asthma attacks: the stiffness of the collagen-based support structure of the airway cells. 

They tested their theory by treating the extracellular matrix of healthy bovine airways with vitamin B2 and ultraviolet A radiation to stiffen the structure. Called collagen crosslinking, the procedure is often performed to stiffen the collagen in the cornea during eye surgery. The goal was to show how an asthma trigger could cause airway constriction in the absence of inflammation.  

Results showed that when confronted by a trigger, the stiffened bovine airways did indeed constrict, leading the investigators to conclude that stiffening airways in and of themselves can contribute to an asthma attack. They believe a treatment that targets the stiffness of the extracellular matrix could hold potential as a new asthma therapy.  

The study was published by the Journal of Applied Physiology in June.  

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Smokers Need Angioplasty and Stenting a Decade Before Nonsmokers

If you’re looking for another reason to convince your patients to quit smoking, researchers from Michigan Medicine have provided one. Their statewide study showed that smokers needed procedures to unblock their arteries almost ten years before nonsmokers.  

The research was conducted among patients participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium. None had a history of a heart attack, but they all required angioplasty and/or stenting to widen their coronary arteries and restore blood flow.  

People who were obese needed their procedures four years earlier than those who were not obese.  

“Smoking is a completely preventable risk factor,” said senior author Devraj Sukul, MD, MSc. “If we direct additional efforts at preventing smoking and obesity, we could significantly delay the onset of heart disease and the need for angioplasty and stenting.” 

The study was published by PLOS One in June.   

Nanoparticles Deliver Meds Directly to the Lungs

Nanoparticles that mimic immune cells are being used at the University of California San Diego to target inflammation in the lungs. Researchers have tested the concept by filling the nanoparticles with dexamethasone and delivering them into the inflamed lungs of mice. Following the treatment, the inflammation was reversed. What’s more, the drug concentration used was lower than what would have been required for standard administration. 

“We’re delivering the exact same drug used in the clinic, but the difference is we’re concentrating the drugs to the point of interest,” said study author Joon Ho Park. “By having these nanoparticles target the inflammation site, it means a larger portion of the medicine will wind up where it’s needed, and not be cleared out by the body before it can accumulate and be effective.” 

The next step, say the investigators, is to test the process using human cell membranes. The study was published by Science Advances on June 16.  

MSC Treatment May One Day Benefit Pulmonary Fibrosis Patients

Microgel-coated mesenchymal stromal cells (MSCs) were shown to reverse fibrosis and promote tissue repair in a study conducted by University of Illinois Chicago researchers.  

The thin microgel coating boosted the therapeutic potential of MCSs, which have been studied as a treatment for fibrosis, to degrade scar tissue and regenerate healthy tissue in mouse models of fibrosis. The investigators believe the treatment may one day benefit patients with pulmonary fibrosis. 

“While previous studies tested the therapeutic effects of MSCs — which are known to suppress inflammation and to adapt to different tissue environments — their efficacy has so far been limited to early phases of the disease, when inflammation levels are high and scar tissue is still forming,” said study author Jae-Won Shin. “Our approach was to optimize MSC-based therapeutics to work after inflammation has been reduced, which is when most people are diagnosed with fibrosis.” 

The paper appeared in a recent edition of Nature Biomedical Engineering. 

Email newsroom@aarc.org with questions or comments, we’d love to hear from you.

Debbie Bunch

Debbie Bunch is an AARC contributor who writes feature articles, news stories, and other content for Newsroom, the AARC website, and associated emailed newsletters. In her spare time, she enjoys reading, traveling, photography, and spending time with her children and grandchildren. Connect with Debbie by email or on AARConnect or LinkedIn.

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