Novel methods (e.g., delivery systems, high-throughput screening, precision/personalized medicine) as well as pre-clinical in vitro (e.g.
organoids/spheroids, induced pluripotent stem cells, conditional reprogrammed primary airway epithelial cells) and in vivo models (e.g., CF mouse/rat, rabbit, ferret, pig) have emerged to optimize the experimental and clinical phases of therapy development including; CFTR modulators, ENAC inhibitors, activation of alternative chloride channels, new antibiotics/anti-inflammatories/mucolytics, phage therapy, cell-based and gene-based therapies.
Background and History of Cystic Fibrosis Research Cystic Fibrosis is a disease caused by genetic mutations, effecting more than 300 million people worldwide, that causes a buildup of mucus in the alveoli of the lungs (CF Foundation).
This disease is so detrimental because viscous mucus coats the alveoli, severely obstructing breathing and preventing the exchange of oxygen and carbon dioxide in the lungs at times.
These infections occur so frequently because the warm, viscous mucus forms a sustainable environment for bacterial colonies to grow.
Amoxicillin or Erythromycin can cure the bacterial infections, but there is no known genetic cure for CF.Once considered a childhood disease, over half of those living with CF in the United States are over the age of 18.While life expectancy for those recently diagnosed has reached the mid-forties, the median age of death remains only thirty years.The filled with mucus due to Cystic Fibrosis (CF Foundation).symptoms for CF include persistent coughing 1 episodes, shortness of breath, buildup of phlegm, salty tasting skin, poor weight gain, male infertility, and frequent Staphylococcus aureus, Haemophilus influenzae, and Pneumonia aeruginosa infections, (CF Foundation).In this line, a vicious cycle of mucus accumulation in the airways, chronic inflammation, and recurrent infections, leads to permanent tissue damage and airway remodeling, and eventually end-stage lung disease later in life.Over the last decades, life expectancy of CF patients has lengthened, thanks to early diagnosis and more effective therapies; however, patients still face limited quality of life and significantly reduced life expectancy.Therefore, recombination of DNA between the JG2E1 and E2.6 spots cause the deletion of phenylalanine in translation. The second molecular process of Cystic Fibrosis, quorum sensing in the formation of biofilms, makes Pneumonia aeruginosa infections caused by CF almost impossible to treat. aeruginosa forms is nearly unresponsive to antibiotics (Keivit et al., 2001). aeruginosa has two quorum sensing systems, Las and Rhl, where autoinducer molecules, abbreviated AI are released by each cell. Cystic Fibrosis was originally thought to be caused by bacterial infections alone, until the CF gene was discovered on human chromosome seven in 1989 (CF Foundation).Early research led to the conclusion that CF was caused by a mutation in paroxonase, a series of enzymes that control the hydrolysis of organophosphates (Knight and Hodson, 1990).