scholarly journals Sustained Glycemic Control With Ivacaftor in Cystic Fibrosis–Related Diabetes

2019 ◽  
Vol 7 ◽  
pp. 232470961984289 ◽  
Author(s):  
Francis Christian ◽  
Andrew Thierman ◽  
Erin Shirley ◽  
Karen Allen ◽  
Cory Cross ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Glycemic Control ◽  
Pancreatic Insufficiency ◽  
Disease Process ◽  
Current Treatment ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Endogenous Insulin ◽  
Short Period

Cystic fibrosis–related diabetes (CFRD) is a common comorbidity in cystic fibrosis with pancreatic insufficiency occurring early in the disease process. Current treatment is exogenous insulin therapy as CFRD is due to impaired insulin secretion. Recent small studies have shown improvement in endogenous insulin secretion with a short period of ivacaftor therapy in primarily pediatric patients with cystic fibrosis transmembrane conductance regulator mutations amenable to potentiation. In this article, we present the case of an adult patient with long-standing CFRD who developed sustained improvement in glycemic control after initiation of ivacaftor.

scholarly journals “Pathogen Eradication” and “Emerging Pathogens”: Difficult Definitions in Cystic Fibrosis

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Peter H. Gilligan ◽  
Damian G. Downey ◽  
J. Stuart Elborn ◽  
Patrick A. Flume ◽  
Sebastian Funk ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Inflammation ◽  
Airway Disease ◽  
Current Treatment ◽  
Transmembrane Conductance Regulator ◽  
Common Complication ◽  
Emerging Pathogens ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Chronic Use

ABSTRACTInfection is a common complication of cystic fibrosis (CF) airway disease. Current treatment approaches include early intervention with the intent to eradicate pathogens in the hope of delaying the development of chronic infection and the chronic use of aerosolized antibiotics to suppress infection. The use of molecules that help restore CFTR (cystic fibrosis transmembrane conductance regulator) function, modulate pulmonary inflammation, or improve pulmonary clearance may also influence the microbial communities in the airways. As the pipeline of these new entities continues to expand, it is important to define when key pathogens are eradicated from the lungs of CF patients and, equally important, when new pathogens might emerge as a result of these novel therapies.

Treating the Underlying Cystic Fibrosis Transmembrane Conductance Regulator Defect in Patients with Cystic Fibrosis

2019 ◽  
Vol 40 (06) ◽  
pp. 762-774 ◽  
Author(s):  
Senne Cuyx ◽  
Kris De Boeck
Keyword(s):  
Cystic Fibrosis ◽  
Significant Proportion ◽  
Real Life ◽  
Current Treatment ◽  
Detailed Knowledge ◽  
Transmembrane Conductance Regulator ◽  
Class Iii ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

AbstractDetailed knowledge of how mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disturb the trafficking or function of the CFTR protein and the use of high-throughput drug screens have allowed novel therapeutic strategies for cystic fibrosis (CF). The main goal of treatment is slowly but surely shifting from symptomatic management to targeting the underlying CFTR defect to halt disease progression and even to prevent occurrence of CF complications. CFTR potentiators for patients with class III mutations, mutation R117H (and in United States also for patients with specific residual function mutations) and the combination of a CFTR modulator plus a potentiator for patients homozygous for F508del, are the two classes of modulators that are in use in the clinic. Approval of these therapeutics has progressively expanded to include both younger patients and a wider range of CFTR mutations. For a significant proportion of patients with CF, current treatment is however still insufficient or unavailable.This review provides an overview of the clinical trial results and the real-life efficacy data of approved CFTR modulators. In addition, we discuss the entire pipeline of CFTR modulators: novel potentiators and correctors, amplifiers, stabilizers, and read-through agents. Furthermore, we discuss other strategies to improve CFTR function like nonsense-mediated decay inhibitors, modified transfer ribonucleic acids, antisense oligonucleotides, and genetic therapies.CFTR modulators are already changing the face of CF and the pipeline of new therapies continues to be exciting.

scholarly journals Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

2008 ◽  
Vol 42 (4) ◽  
pp. 389-412 ◽  
Author(s):  
I Kukavica-Ibrulj ◽  
R C Levesque
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Animal Models ◽  
Pancreatic Insufficiency ◽  
Lung Infection ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Human Form ◽  
Cftr Protein ◽  
Chronic Lung Infection

Summary Cystic fibrosis (CF) is caused by a defect in the transmembrane conductance regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the CFTR protein results in salty sweat, pancreatic insufficiency, intestinal obstruction, male infertility and severe pulmonary disease. In most patients with CF life expectancy is limited due to a progressive loss of functional lung tissue. Early in life a persistent neutrophylic inflammation can be demonstrated in the airways. The cause of this inflammation, the role of CFTR and the cause of lung morbidity by different CF-specific bacteria, mostly Pseudomonas aeruginosa, are not well understood. The lack of an appropriate animal model with multi-organ pathology having the characteristics of the human form of CF has hampered our understanding of the pathobiology and chronic lung infections of the disease for many years. This review summarizes the main characteristics of CF and focuses on several available animal models that have been frequently used in CF research. A better understanding of the chronic lung infection caused particularly by P. aeruginosa, the pathophysiology of lung inflammation and the pathogenesis of lung disease necessitates animal models to understand CF, and to develop and improve treatment.

scholarly journals The role of insulin analogues in the current treatment of diabetes mellitus

2006 ◽  
Vol 59 (11-12) ◽  
pp. 539-544 ◽  
Author(s):  
Milena Mitrovic ◽  
Pavle Pantelinac ◽  
Jovanka Radosavljevic ◽  
Ivana Bajkin ◽  
Ljiljana Todorovic-Djilas
Keyword(s):  
Insulin Secretion ◽  
Glycemic Control ◽  
Human Insulin ◽  
Basal Insulin ◽  
Current Treatment ◽  
Insulin Analogues ◽  
Endogenous Insulin Secretion ◽  
Neutral Ph ◽  
Endogenous Insulin ◽  
Rapid Action

Introduction. Ever since insulin was discovered by Banting and Best in 1921, all further researches in this field had been conducted with one goal: to find new insulin molecules which would provide better glycemic control with fewer side effects i.e. to mimic endogenous physiological insulin secretion. Normal insulin secretion. In healthy individuals, endogenous insulin secretion can be classified as basal (which provides basal glucose homeostasis) and stimulated (as a response to a meal). Conventional insulin preparations - human insulin, have time-action profiles that cannot fully imitate endogenous insulin secretion, thus leading to postprandial hyperglicemia and high glycemic oscilations during the day. Rapid-acting analogues. Rapid acting analogues should have a time-action profile with onset of less than one hour, duration less than four hours, hypoglycemic potency equal or greater than that of human insulin, and similar effects in all patients. Two rapid action analouges, lispro and aspart are available. Basal insulin analogues. The ideal basal insulin should provide slow and constant absorption, long half-life that would provide once daily dosing (or every other day), and peakless effect. Insulin glargine led to solubility at pH 4 and to slow absorption in neutral pH environment. Insulin detemir is a soluble insulin analogue with neutral pH and affinity to bind to serum albumin, thus gaining prolonged action. Mitogenic influence. The mitogenic influence of insulin is due to the affinity to bind to IGF-1 receptors. Following two-year administration of glargine in mice and rats, systemic carcinogenic potential was not found, though there were reports of hepatocellular carcinomas, which are frequently found in these animals. Conclusion. In the last two decades, many trials have shown that unsatisfactory glycemic control leads to chronic complications in both types of diabetes. Using basal glucose level, postprandial glycemy and HbA1c as matabolic parameters, it has been proven that only strict glycemic control can lower the risk of developing complications. Discovery of insulin analogues (both rapid acting and basal) enables physicians to provide better glycoregulation and less hypoglycemic incidents to their patients. .

scholarly journals Cystic fibrosis: current treatment and future direction

2021 ◽  
Vol 10 (4) ◽  
pp. 444
Author(s):  
Shreya Gupta ◽  
Niti Mittal ◽  
Mahesh C. Gupta
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channels ◽  
Genetic Disorder ◽  
Pancreatic Insufficiency ◽  
Genetic Defect ◽  
Disease Process ◽  
Holistic Approach ◽  
Current Treatment ◽  
Cftr Gene ◽  
Long Term Effects

Cystic fibrosis is an autosomal recessive genetic disorder, characterized by mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to abnormality in the chloride channels of the mucus and sweat producing glands. Multiple organs systems are affected in this disorder, like respiratory system and gastrointestinal tract, severely impacting the patient’s quality of life, eventually leading on to several complications and death. Since the uncovering of the underlying genetic defect in cystic fibrosis (CF), our knowledge of the disease process has increased substantially, but we still lack a holistic approach to its management, which comprises of multiple facades, requiring both pharmacological and non-pharmacological or rehabilitatory approaches. So far, the therapeutic options were limited to targeting the consequences and complications of the disease, such as respiratory infection, mucus retention, pancreatic insufficiency, etc., but now several promising therapies may be able to address the underlying pathology rather than its long-term effects. This review summarizes the current and upcoming pharmacological options for CF, such as those targeting the CFTR gene defect directly, including gene editing, CFTR correctors and potentiators; drugs targeting the epithelial sodium channels (ENaC inhibitors); repositioning of some existing drugs and evaluating their role in CF; and understanding the disease better by transcriptomic approaches and the role of gut microbiota in the disease process and severity.

Drug Optimization for Cystic Fibrosis Patients Based on Disease Pathways Crosstalk

2021 ◽  
Vol 11 (1) ◽  
pp. 1-11
Author(s):  
Shuting Lin ◽  
Yifei Wang
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Cftr Gene ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Dna Mutations ◽  
Pathway Crosstalk ◽  
Disease Modifier ◽  
Drug Optimization ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is a common autosomal recessive disease characterized by pancreatic insufficiency and progressive deterioration of lung function. It has been shown that CF is caused by the presence of mutations in both alleles at the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The severity of CF disease reflects the change of molecular mechanism, including DNA mutations on CFTR gene and polymorphic variations in disease modifier genes. Better understanding the differences among different CF severity group is helpful for improving therapeutic plans for patients. In this paper, the authors present a computational network biology approach to screen precision drugs for CF patients, which is based on the intensity of drugs impact on the pathway crosstalk mediated by differential methylation genes. The results indicate that ivacaftor, tezacaftor, and lumacaftor are applicable to all severity cohorts, gefitinib, sorafenib, sunitinib, and imatinib mesylate have the potential to treat intermediary CF patients, and tamoxifen may be useful to mild and sever CF patients.

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