Kalydeco: A Quinolone Carboxyamide Small Molecule Drug

Cystic Fibrosis (CF) is an autosomal recessive genetic disease that causes thickened mucus to form in the lungs, pancreas, and other organs. It affects a specific protein called Cystic Fibrosis Transmembrane Regulator (CFTR) that controls the normal movement of sodium, chloride, and water in and out of the cells within the body. Those diagnosed with CF have either too little or abnormal CFTR. When CFTR is absent or defective, the mucus usually secreted by the cells in the pulmonary airways, pancreatic ducts, and gastrointestinal tract become thickened, leading to obstructions, frequent infection, and loss of function in the affected organs (Cystic Fibrosis Symptoms, Causes & Risk Factors, 2018). According to the Cystic Fibrosis Foundation

Cystic Fibrosis is a genetic disease which is progressive and limits breathing ability. The lungs and other organs are affected by a thick buildup of mucus. This mucus traps bacteria which leads lung damage, infections, and respiratory failure. The digestive enzymes being released is prevented, affecting the breakdown of food and nutrients being absorbed. ?More than 30,000 children and adults in the United States have Cystic Fibrosis. 70,000 people worldwide.? (Diagnosed With Cystic Fibrosis, Cystic Fibrosis Foundation) Someone who has Cystic Fibrosis have a defective gene from each parent which produces faulty protein. The CFTR gene is the gene that is mutated causing this. The channel that transports chloride in and out of cells is created by instructions that are created by CFTR gene. The regulation of chloride ions and water are prevented creating the thick mucus formed on the passageways of lungs, pancreas, and other organs. Cystic Fibrosis doesn?t cause learning problems are mobility of the person. Babies with this still develop and grow up normally. The average life expectancy is close to 40 years, and has been increasing in the last fifty years thanks to improved care. ?Chronic coughing, recurring chest colds, wheezing, shortness of breath, frequent sinus infections, and allergies that last all year, are the most common symptoms of Cystic Fibrosis.? (Cystic Fibrosis Symptoms) Since this disease is progressive

What is Cystic Fibrosis? How does it affect people living with it? Cystic Fibrosis, also known as CF, is a life-threatening hereditary disease. It is inherited by a faulty cystic fibrosis transmembrane conductor (CFTR) gene from each parent (Kowalczyk, 2014, p. 74). This faulty gene makes a defective protein that does not work well and causes the body to produce sticky, thick mucus and very salty sweat("About CF: Causes, Signs & Symptoms of Cystic Fibrosis,"

Cystic fibrosis (CF) is an inherited disease that affects the lungs and digestive system (National Heart, Blood, and Lung Institute, 2013). CF is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7q31 (Beery & Workman, 2012, p. 192). More than 1600 different mutations in this gene have been identified, but 70% of cystic fibrosis patients have the amino acid ΔF508 defect. This mutation occurs when the CFTR protein is missing three nucleotides at position 508 which codes for the amino acid phenylalanine essential to nutrition (Scott, 2013, p. 493).

For centuries, genetic diseases have raided the planet growing stronger and mutating faster every day. Scientists have been working hard to develop concoctions to reduce the crippling effects of these diseases; if not eradicate the harsh effects of these potentially deadly genetic conditions altogether. Among these numerous life threatening genetic diseases is cystic fibrosis (CF), an inherited lifelong condition that promotes the production of thick sticky mucus causing lung infections from the entrapment of various bacteria such as Pseudomonas aeruginosa.

The type of mutation that causes Cystic Fibrosis occurs in the CFTR gene, or Cystic Fibrosis Transmembrane Conductance Regulator gene. This gene is important to the body because it helps provide channels that transport negatively charged particles (chloride ions) in and out of the cell. Chloride has an important role in the human body by how it controls the movement of water in tissue, which allows mucus to become thin. Mutations in the CFTR gene interrupts the function of the chloride channels. It makes the regulating process of the flow of chloride ions and water across the cell membranes not happen. This causes passageways to produce mucus that is very thick. The thick mucus causes these passageways to clog, and trap

​Cystic fibrosis is an inherited, chronic disease of the secretory glands which directly affects the lungs and digestive system (NLM, 2015). To look more closely at a cellular level, there is a defective gene in which their protein product that regulates movement of sodium

Cystic Fibrosis is an inherited disease caused by mutations in a gene on 7th pair of chromosomes. Cystic Fibrosis is a chromosomal abnormality, meaning that one of the 23 pairs of chromosomes are not what they are supposed to be. A person without Cystic Fibrosis has a gene in chromosome 7, which produces a normal and substantial amount of protein called Cystic Fibrosis transmembrane regulator (CFTR), which in turn produces thin and watery mucus. A person with Cystic Fibrosis has a gene in chromosome 7, which produces either abnormal CFTR protein or no CFTR protein at all, which causes the body to produce thick and sticky mucus “A person with CF produces abnormal CFTR protein — or no CFTR protein at all, which causes the body to make thick,

Cystic Fibrosis (CF) also knows as (mucoviscidosis) is a single-gene disorders. This disorder is best described as an autosomal recessive of the exocrine glands. The disorder itself can be categorized as either pus- forming or hindering airflow. The responsible gene for this pulmonary disorder has been discovered to the be on the long part of the arm of chromosome 7 (Copstead & Banasik, 2013). Major signs and symptoms of CF will be associated with the gastrointestinal and respiratory system. We are able to diagnose CF though laboratory testing such as arterial blood measurements. Treatments for CF tend to be comprehensive including specialty physicians, nutritionists, physical and respiratory therapists and genetic counselors. Medicare

Cystic fibrosis (CF), is an autosomal recessive disorder [figure 1.], caused by a mutation in two genes on chromosome 7 – the genes responsible for the way water and salts pass in and out of the cells in the body. CF affects the secretion and reabsorption of chloride ions, producing a much thicker than normal layer of mucus (in the lungs, pancreas and liver primarily) that is ideal for bacteria and infection to flourish. The faulty gene may fail to produce the cystic fibrosis transmembrane conductance regulator (CFTR) protein or may produce the protein however this protein is faulty is such a way that it does not regulate chloride secretion and reabsorption properly or at all. Currently there are a wide array of

This protein is in charge of the movement of water and sodium ions through channels, giving substances like mucus a thick or thin concentration by moving the substances through the channels as needed (Cystic Fibrosis, 2015). Though it is known as a gene that can cause cystic fibrosis, it is not the only condition that can be a result of this mutation and if a mutation is found on this gene it is not a definite result that the child will have CF and will need further testing in order to determine what the physical manifestation of the mutation will be (Cystic Fibrosis,

According to the Cystic Fibrosis Foundation, approximately 70,000 people worldwide suffer from cystic fibrosis, 30,000 of which live in the United States. Within the U.S., 1,000 new cases are diagnosed each year and more than 75 percent are diagnosed by the age of two (“About Cystic Fibrosis, n.d.). CF “is an autosomal recessive lung disease that decreases the ability of chloride channels to function properly. This inherited chloride channel defect results in decreased salt levels through sweat loss” (Delaney, 2014, p. 682). This decrease in salt levels “leads to thickened secretions, predominantly in the lung and pancreas, and is characterized by recurrent lung infections, malabsorption of nutrients, intestinal obstruction, liver disease and infertility in males” (Richards, 2008, p.35). Developments in the treatment of CF have increased the median life expectancy for patients with the disease, but with increasing age there becomes “a blockage of the exocrine ducts in the pancreas resulting in a form of diabetes, known as cystic fibrosis-related diabetes (CFRD)” (Richards, 2008, p.35). Of all the possible complications related to cystic fibrosis, CFRD is “the most prevalent co-morbidity” and is associated with increased hospitalization rates, decreased pulmonary function, and weight loss (Delaney, 2014, p.682 and Kelly & Moran, 2013).

Cystic Fibrosis (CF) is an autosomal recessive gene that causes a wide range of symptoms because there are over 1,000 changes or mutations that can occur within the cystic fibrosis transmembrane receptor (CFTR) protein. The CFTR protein is generally a chloride ion chain “regulated by cyclic adenosine monophosphate and therefore can act as a regulator of other electrolyte channels”(Grossman, S., & Grossman, L. 2005, p. 46). Typically this protein allows chloride ions to exit mucus-producing cells allowing water to flow in and thin the mucus. However, if the CFTR protein has been mutated, such as in cystic fibrosis, chloride ions cannot exit. This causes the mucus to thicken, become sticky, and obstruct the various channels it passes through. This build up of mucus also prevents bacteria from being cleaned from cells thoroughly increasing the patients risk for infections (Grossman, S., & Grossman, L. 2005). However, the severity of CF depends on whether the patients have complete or partial loss of the CFTR gene. If the person has the classic form of CF abnormalities of CFTR will commonly affect “…the respiratory, gastrointestinal, endocrine and metabolic, and genitourinary systems”(Schram, C. 2012). However, if people have atypical forms of CF their genetic disorder may only affect one of the organ systems and may not be found until the patient develops symptoms in their late childhood, early adolescence, or adulthood

Cystic Fibrosis is caused by a genetic defect in Chromosome 7. Chromosome 7 encodes the cystic fibrosis transmembrane conductance regulator, also known as CFTR. There are over 1,000 mutations of this gene causing cystic fibrosis, with each mutation manifesting as a different variation of disease onset and clinical presentation. The most common mutation is the loss of phenylalanine residue at deltaF508. The abnormal functioning CFTR causes impaired chloride transport and more viscous secretions. The defect causes dehydrated secretions in the respiratory tract and gastrointestinal tract. Being dehydrated, these secretions become more difficult to move throughout the body. Along with impaired

The inhibition of sodium absorption through the epithelial sodium channel is a substitute method to CFTR pharmacotherapy. This technique is supported by evidence that mice who overexpress the β subunit of the epithelial sodium channel and consequently have sodium hyper absorption contain signs of cystic fibrosis lung disease, such as neutrophilic inflammation and mucus plugging mucus plugging. In clinical trials, amiloride (an epithelial sodium channel blocker with a short half-life) along with having no clinical advantage, it exhibited a trend toward deteriorated lung function in the treated patients. Progressively, studies with the epithelial sodium channel mouse model established that amiloride had inadequate efficacy when administered after airway disease had advanced, whereas premature administration prohibited the development of lung disease. So far, in vivo data from humans are lacking to support this concept. Amiloride has a short half