Top 10 Cystic Fibrosis Stories of 2022
Trikafta, gene therapy, and COVID-19 are among the year's hot topics for readers
Cystic Fibrosis News Today brought you daily coverage of the latest scientific discoveries, treatment advances, and clinical trials related to cystic fibrosis (CF) this past year.
We look forward to continuing to offer you the most up-to-date information in 2023. Here are the 10 most-read CF news articles of 2022, with a brief description of what made them relevant to our readers.
No. 10 – “Trikafta Reduces Harmful Microbial Load in CF Airways After 1 Year”
A year of treatment with Vertex Pharmaceuticals’ triple combo CFTR modulator therapy Trikafta (elexacaftor, tezacaftor, and ivacaftor) was found to significantly reduce the abundance of harmful microbes in the airways of CF patients in a small study.
Pseudomonas aeruginosa and Staphylococcus aureus, two common bacteria known to drive CF lung infections, were diminished with treatment, while overall microbial diversity was improved.
As early as three months after starting Trikafta, patients also saw gains in body weight and lung function.
No. 9 – “Aerosolized Therapy Restores CFTR in Patient-derived Cells”
In May, researchers from ReCode Therapeutics presented data demonstrating that its aerosolized RNA-based therapy restored CFTR function — the protein that’s faulty in CF — in patient-derived lung cells.
The therapy uses the company’s selective organ targeting lipid nanoparticle platform to deliver CFTR messenger RNA — the template molecule that carries genetic instructions for making protein — directly to the airways, where production of a healthy CFTR protein is facilitated.
Improvements were observed in cells from patients with several different types of CF-causing mutations, some of which are not responsive to Trikafta.
No. 8 – “Kaftrio Approved for Children Ages 6 and Up in European Union, UK”
At the start of year, the European Commission expanded approval of CFTR modulator Kaftrio (ivacaftor/tezacaftor/elexacaftor), in a combination regimen with Kalydeco (ivacaftor), to include children as young as 6 years, who have at least one copy of F508del, the most common CF-causing mutation.
The Medicines and Healthcare Products Regulatory Agency in the U.K. approved a similar expansion.
Kaftrio had previously been approved in these countries for patients 12 and older. The treatment is also approved for patients 6 and up in New Zealand, Switzerland, Canada, and the U.S., where it’s marketed as Trikafta.
No. 7 – “Trikafta After CF Lung Transplant: Not Well-tolerated, Modest Benefits”
A small study found that one year of Trikafta treatment after lung transplant resulted in limited improvements in sinus and digestive problems, and was not well-tolerated.
Nearly 40% (5 of the 13 patients) in the study permanently stopped treatment sooner than a year, citing reasons including lung function declines, mood disturbances, and lack of perceived benefit. For the other patients, some reductions in sinus symptoms and digestive problems were reported.
The researchers noted that the complexity of the patients’ post-transplant care and the low number of participants involved in the study mean that the results could not be considered conclusive.
No. 6 – “CFTR Protein Defects May Work to Protect Against Severe COVID-19”
Researchers in Italy found that human airway cells housing the F508del mutation were better able to limit the replication and spread of SARS-CoV-2, the virus that causes COVID-19, than healthy cells.
In turn, recovery of more normal CFTR function with CFTR modulators led to increased viral replication.
The findings offer insight into observations that CF patients tend to have mild COVID-19 symptoms, despite expectations that they would be susceptible to severe infection, the researchers noted.
No. 5 – “CF Carrier Prevalence May Factor in Variability in COVID-19 Outcomes”
Another research team found that a higher prevalence of CF, as an indicator of the number of CF carriers, was correlated with higher rates of COVID-19 and related mortality during the early stages of the pandemic.
CF carriers have one mutated copy of the CFTR gene, which means that they do not develop CF, but can pass the mutated gene to their children, who may develop the condition if they inherit a second mutated copy from their other biological parent.
The research, involving 37 different countries, came as an effort to understand why the spread and impacts of COVID-19 differed so significantly by geographical region. Researchers note that while more work is needed, the findings suggest a contribution of CFTR in COVID-19 disease processes.
No. 4 – “Reducing Trikafta Dose May Ease Mental Side Effects, Study Reports”
A study from the U.K. found that lowering the dose of Trikafta while providing psychological support could ease known mental health side effects of the treatment, including depression, anxiety, and brain fog. The findings could mean that patients do not need to stop treatment entirely should they experience such side effects, the study’s researchers said.
Since most patients in the study had previously used Symdeko, a combination of tezacaftor and ivacaftor, without experiencing mental health problems, the researchers suspected that Trikafta’s third ingredient — elexacaftor — was likely causing the symptoms.
No. 3 – “ ‘Salt in My Soul’ Now a Film About Mallory Smith’s Life With CF”
In early 2022, the posthumously published memoir of Mallory Smith, a young woman with CF who died from an antibiotic-resistant infection after lung transplant, premiered as a documentary. Titled “Salt in My Soul: An Unfinished Life,” the documentary chronicles Smith’s battle with CF from the time of her diagnosis at age 3 to her death in 2017 at age 25.
After her death, her mother, Diane Shader Smith, was allowed access to the journals she kept from ages 15–25, which formed the basis of the memoir.
All money made from the film will go to Mallory’s Legacy Fund, which supports clinical research into antibiotic-resistant superbugs.
No. 2 – “Gene Editing Corrects CF Mutation in Multiple Organs All at Once”
In a preclinical study, researchers developed a new gene-editing platform that could correct the CF-causing F508del mutation across multiple different tissues in mice.
Simply put, the treatment consists of tiny nanoparticles containing molecules called peptide nucleic acids that work to prompt the body’s normal DNA-repairing machinery to fix a mutation, thereby restoring more normal CFTR function.
When delivered into the bloodstream, the treatment made its way into the lungs, digestive tract, and other organs, where it led to increased CFTR function without causing notable toxicity. Further optimization of the delivery platform is still needed to make the treatment a “one-time cure,” according to the researchers.
No. 1 – “First Patient Dosed in Trial of Aerosol-delivered Genetic Medicine”
Our most-read article of 2022 announced the dosing of the first patient in a Phase 1/2 clinical trial of 4D-710, the inhaled gene therapy being developed by 4D Molecular Therapeutics for CF. The open-label study (NCT05248230) is testing the treatment’s safety, tolerability, and preliminary effectiveness in adults with CF at sites in the U.S.
4D-710 is designed to work for patients regardless of their specific CF-causing mutation. Administered as an aerosol, it works to provide a healthy copy of the CFTR gene directly to the cells that line the airways, thereby promoting the production of a working CFTR protein.
Interim trial results presented at a conference in November showed that a single dose of the treatment was safe and restored CFTR protein production in the lungs of three participants. A second, higher dose is being tested in another group of participants. Lung function tests and quality of life are being monitored for a year after dosing.
The trial is expected to finish in August 2025.
At Cystic Fibrosis News Today, we hope these stories and our reporting in 2023 contribute to informing and improving the lives of those living with CF, and their loved ones.
We wish all our readers a happy new year!