When two channels that are supposed to move chloride and sodium ions out of cells in the lungs fail to function properly, it leads to the mucus buildup seen in cystic fibrosis.
Japanese researchers have discovered that the channel dysfunctions also reduce the amount of zinc ions going into the lungs, further contributing to the thick mucus accumulation.
Their study, published in the journal EBioMedicine, is titled “Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells.” Continue reading Low Level of Zinc Ions in Lungs Contribute to Buildup of Mucus in CF
Arch Biopartners recently completed a good manufacturing practice (GMP) production campaign for AB569, a potential inhalation treatment for antibiotic-resistant bacterial lung infections in people with cystic fibrosis (CF) chronic obstructive pulmonary disease (COPD) and other conditions. The campaign, intended to ensure the quality of the investigative therapy, was directed by Dalton Pharma Services.
AB569 is composed of ethylenediaminetetraacetic acid (EDTA) and sodium nitrite, two compounds approved by the U.S. Food and Drug Administration (FDA) for use in people. AB569 can be administered alone or in combination with other compounds to treat multi-drug resistant bacterial infections that can cause reduced lung function.
Pseudomonas aeruginosa is one of the most common bacterial infections in patients with respiratory diseases, including CF, COPD, and pneumonia.
In preclinical studies, AB569 was shown to be capable of killing drug-resistant bacteria like P. aeruginosa and other common pathogens associated with chronic lung infections.
The company also announced that a Phase 1 clinical trial to investigate the safety and pharmacokinetic profile of AB569, planned to start in January, will be conducted at the Cincinnati Veterans Affairs Medical Center (CVAMC). According to an Arch Biopartners press release, Ralph Panos, chief of medicine at CVAMC, will lead the trial.
Three escalating doses of nebulized AB569 will be used to evaluate tolerance to the treatment in about 25 healthy volunteers. Each will be given a single administration of nebulized AB569 to characterize the pharmacokinetic profile of plasma nitrite and nitrate metabolites, exhaled nitric oxide, and circulating hemoglobin.
Pharmacokinetics studies how a drug is absorbed, distributed and metabolized in, and expelled by, the body.
Should the Phase 1 trial in volunteers be successful, Arch Biopartners plans to move its AB569 program into a Phase 2 trial to test its effectiveness in treating chronic P.aeruginosa infections in COPD patients.
AB569 received orphan drug status by the FDA in November 2015 as a potential treatment of P. aeruginosa lung infections in CF patients. Orphan drug status is given to investigative medicines intended for people with rare diseases to speed their development and testing.
Researchers from the University of Zurich have determined the structure of a chloride channel, which could be a target for new drugs to treat cystic fibrosis.
Researchers at the University of Zurich have found a new target for future cystic fibrosis treatments. The study, published in Nature, has uncovered the structure of a protein that could help to correct the mechanism underlying the buildup of sticky mucus in patients’ lungs. This could give rise to a new wave of therapeutics for the condition, which at the moment lacks disease-modifying treatments.
Cystic fibrosis is a severe genetic disease affecting the lungs, for which there is currently no cure. It is caused by a malfunctioning chloride channel, CFTR, which prevents the secretion of chloride by cells, leading to the production of thick, sticky mucus in the lung. The condition affects around 70,000 people worldwide, who suffer from chronic infections and require daily physiotherapy.
However, one potential approach to treat cystic fibrosis is to activate the calcium-activated chloride channel, TMEM16A, as an alternative route for chloride efflux. As TMEM16A is located within the same epithelium as CFTR, its activation could rehydrate the mucus layer. The research group used cryo-electron microscopy to decipher the structure of TMEM16A, which is part of a protein family that facilitates the flow of negatively charged ions or lipids across the cell membrane.
TMEM16A is found in many of our organs, playing a key role in muscle contraction and pain perception, as well as in the lungs. It forms an hourglass-shaped protein-enclosed channel, which when bound by positively charged calcium ions, opens to let chloride ions to pass through the membrane.
Current treatments for cystic fibrosis include bronchodilators, mucus thinners, antibiotics, and physiotherapy, which only control symptoms. However, biotechs around Europe are beginning to make progress, with ProQR completing a Phase Ib trial and Galapagos and Abbvie’s triple combination therapy entering Phase I. Antabio has also received €7.6M from CARB-X to develop a new antibiotic against Pseudomonas infections.
The identification of a new target provides patients and biotechs alike with renewed hope of new and effective cystic fibrosis treatments, or even a cure. It will be interesting to see whether small molecules or gene therapy specialists could take advantage of this information.
Original article: https://labiotech.eu/cystic-fibrosis-treatment-target/
I’m not naïve enough to think that I’m going to wake up tomorrow and find that my life is moving forward with cystic fibrosis in the rearview mirror.
We’re still a little bit away from that moment, but that doesn’t mean I don’t have high expectations for treatment development. Continue reading My Wish List for the New Year By Gunnar Esiason
An investigation led by the University of Pittsburgh School of Medicine has found a link between a new class of bacterial enzymes and the chronic lung inflammation that plagues patients with cystic fibrosis, a terminal lung Continue reading Pitt study links cystic fibrosis lung inflammation to opportunistic bacteria