A number of important discoveries, therapeutic developments, and events related to cystic fibrosis (CF) were reported daily by Cystic Fibrosis News Today throughout 2016. Now that the year is over, it is time to briefly review the articles that appealed most to our readers. Here are the top 10 most-read articles of 2016, with a brief description of what made them interesting and relevant to CF patients, family members, and caregivers.
The experimental drug Translarna (ataluren), developed by PTC Therapeutics, was reported to make the cellular protein-making machinery run the so-called “stop sign” mutation in the CF-causing CFTR gene, replacing it with amino acids (the protein building blocks) similar enough to allow the protein to do its work. Translarna is now in Phase 3 clinical trials for patients with CF who carry such stop signs, called nonsense mutations, in the CFTR gene.
In a study, scientists found that a combination of two drugs, cysteamine and epigallocatechin gallate (EGCG), may be used to treat CF patients with specific mutations. EGCG was found to alleviate CF symptoms in mice and humans with mutations that only partially damage the cystic fibrosis transmembrane conductance regulator (CFTR) gene (CF is caused by mutations in the gene). Specifically, EGCG improved respiration and reduced signs of inflammation in specific patients, notably those with one or two Phe508del CFTR mutations, but not other mutations.
Researchers discovered why mice that carry CF mutations do not develop the serious lung disease seen in human CF patients, and their work revealed a new therapeutic target that might stop CF progression. When people, mice, and pigs develop CF, the flow of bicarbonate (a base) stops, and the airways become much more acidic. In pigs and people, that decreases the ability to fight infection and, frequently, lung disease. In mice, however, the liquid acidity and susceptibility to infection are not observed. The researchers found that blocking a proton pump, called ATP12A, in the airway tissue of humans and pigs decreases acidity and restores the defense mechanisms against infection. They believe that targeting the pump could be helpful for all types of CF.
A study looked at the abnormalities associated with the rare P67L mutation found in some CF patients, and reported that already two approved drugs, Kalydeco (ivacaftor) and Orkambi (lumacaftor/ivacaftor), reactivated the CFTR channel and treated the abnormalities. The researchers argued that thorough evaluation of rare CFTR mutations offers detailed information that should be considered when developing clinical trials, so as to include individuals with rare forms of CF.
A study reported that toxins produced by mold found on nuts and corn can exacerbate CF and pave the way for airway infections, because they block self-protective mechanisms for the lungs. The toxins, studied by researchers at Perelman School of Medicine at the University of Pennsylvania, are called aflatoxins, and are known to cause cancer and liver damage.
This study reported results from a clinical trial showing that CF patients carrying the F508del mutation in both CFTR gene copies maintained their lung function during more than two years of treatment with the combination drug Orkambi (ivacaftor/lumacaftor). The researchers also found that the treatment lowered the risk of acute exacerbations and improved patients’ weight.
Proteostasis Therapeutics received Fast Track designation from the U.S. Food and Drug Administration (FDA) for PTI-428, an oral modulator in the amplifier class for CF treatment. Amplifiers are CFTR modulators that selectively increase the amount of an immature form of the CFTR protein, providing additional substrate for other CFTR modulators (e.g., correctors or potentiators) to act upon. The Fast Track designation will make developing PTI-428 easier and expedite the review of it as a treatment for CF. The company recently received FDA authorization to start clinical trials of PTI-428 in CF patients.
A new study suggested a method for correcting and improving stem cells derived from CF patients, one that could lead to new ways of treating CF using patients’ cells. To change the CFTR gene, scientists used tiny molecular “scissors,” known as TALENs (transcription activator-like effector nuclease). TALENs can cut and repair a faulty gene in a cell and are able to target and cut specific genes, then repair them in a step-wise process. Using laboratory measurements, the scientists determined that the gene mutation was successfully corrected.
The FDA granted Fast Track designation to QR-010 by ProQR Therapeutics, an inhaled therapy under development to treat CF patients with the ∆F508 mutation in the CFTR gene. The designation will speed the drug’s testing and review. QR-010 is currently being evaluated in two clinical trials in CF patients with this common mutation.
Researchers at the University of Texas in Austin developed a “pure” formulation of the common anti-inflammatory ibuprofen and are working on a way to deliver high doses of the drug directly into the lungs of CF patients as a possible therapy. The researchers will measure ibuprofen concentrations in the lungs and serum of animal models after delivering the ibuprofen particles to the animals’ lungs. Because this is a different application and delivery method of an already approved drug, the development and regulatory approval process should be easier than that for a novel drug.
Cystic Fibrosis News Today hopes that these developments, and new reports coming your way throughout 2017, will ultimately contribute to educate, inform, and improve the lives of patients living with CF.
We wish all our readers a happy and inspiring 2017.