Taking a pill can effectively treat brutal lung disease

Researchers report in Nature Communications they figured out why air sacs in the lungs clog up with a thick substance called surfactant in a brutal disease called Pulmonary Alveolar Proteinosis (PAP), and they show taking cholesterol-busting pills called statins can effectively treat the disease. That's good news for people with PAP because at present the current standard treatment is something called a whole lung lavage. Essentially, it involves flushing patient lungs to clear out the gunk--a procedure so invasive it requires putting people under general anesthesia. Furthermore, the procedure has to be repeated every time the lungs clog up, which translates into some pretty serious quality of life issues for patients.

Researchers at Cincinnati Children's Hospital Medical Center found out the culprit is cholesterol. Led by Bruce Trapnell, MD, director of the Translational Pulmonary Science Center, the team found out years ago that PAP is linked to disruption of cell regulation by a molecule called granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF is crucial for the development of fully mature macrophage cells in the lungs, which are needed to clear away used surfactant - a substance important to lung function - so that people can breathe.

In their new study of PAP patients and mouse models of the disease, the researchers uncovered a more precise reason that disruption of cell regulation by GM-CSF triggers PAP. It's because cell dysregulation reduces the ability of macrophages to process and clear out cholesterol, allowing its levels to build up. This contributes to the accumulation of surfactant that causes PAP and hinders breathing, according to study authors.

"Showing that the pathogenic driver of the disease is disruption of cholesterol homeostasis in these patients will change thinking in the PAP field," explains Trapnell. "Now that we know cholesterol in macrophages is a target for therapeutic development, repurposing statins is a pretty straight forward pharmacological approach for treating people with PAP."

Clinical Trial Planned

The findings are expected to lead to a clinical trial to test statin therapy in larger numbers of people suffering from PAP, said Trapnell. The current study tested statin therapy in two adult patients and in genetically engineered mouse models of PAP.

In both human patients and animal models of PAP, stain therapy was associated with improved cholesterol balance in pulmonary macrophage cells and allowed surfactant to be cleared from lung air sacs. This improved respiratory function in the adult patients and in the laboratory models. Those tests were the result of earlier experiments on mouse pulmonary macrophages and cells donated from patients.

Cormac McCarthy, Elinor Lee, James P Bridges, Anthony Sallese, Takuji Suzuki, Jason C Woods, Brian J Bartholmai, Tisha Wang, Claudia Chalk, Brenna C Carey, Paritha Arumugam, Kenjiro Shima, Elizabeth J Tarling, Bruce C Trapnell.
Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis.
Nature Communicationsvolume 9, Article number: 3127 (2018). doi: 10.1038/s41467-018-05491-z.

Most Popular Now

Compound that kills drug-resistant fungi is isolat…

Antimicrobial and antifungal resistance, which describe the ability of bacteria and other pathogens to resist the effects of drugs to which they were once sensitive, is a...

Novartis receives FDA approval for Mayzent® (sipon…

Novartis today announced that the US Food and Drug Administration (FDA) has approved Mayzent® (siponimod) for the treatment of adults with relapsing forms of multiple scl...

First bacterial genome created entirely with a com…

All the genome sequences of organisms known throughout the world are stored in a database belonging to the National Center for Biotechnology Information in the United Sta...

Immune cells fighting blood cancer visualized for …

When cancer escapes the immune system, our defenses are rendered powerless and are unable to fight against the disease. Chimeric antigen receptor T cells (CAR T cells) re...

Liver, colon cancer cells thwarted by compounds de…

The plant that adds flavor, color and bitterness to beer also produces a primary compound that thwarts cancer cells, and two important derivatives of the compound do as w...

Clinical trial finds therapy to be well-tolerated …

A phase I clinical trial that set out to assess the safety of a new combination therapy for a type of aggressive brain tumour has found the treatment to be well tolerated...

FDA approves treatment for patients with a type of…

The U.S. Food and Drug Administration today approved Cimzia (certolizumab pegol) injection for treatment of adults with a certain type of inflammatory arthritis called no...

Selumetinib granted US Breakthrough Therapy Design…

AstraZeneca and MSD, Inc., Kenilworth, NJ, US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced that the US Food and Drug Administration (FDA) ha...

Boehringer Ingelheim announces FDA and EMA regulat…

Boehringer Ingelheim has filed for regulatory approval of nintedanib in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD) with the FDA and E...

Novartis adds clinical and preclinical anti-inflam…

Novartis announced that it is adding to its broad portfolio of immunomodulatory medicines with the planned acquisition of IFM Tre, a subsidiary of IFM Therapeutics LLC fo...

Novartis continues transformation into a leading m…

Novartis today completed the spin-off of the Alcon eye care devices business through a dividend-in-kind distribution to holders of Novartis shares and ADRs (American Depo...

Forxiga approved in Japan for type-1 diabetes

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Forxiga (dapagliflozin) as an oral adjunct treatment to insulin for adults with type-1 diabetes (T...