Christy L. Shaffer

Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease

P2Y(2) receptor agonists are a new class of compounds that are being evaluated as a treatment for the pulmonary manifestations of Cystic Fibrosis (CF). Results of preclinical research suggest that these compounds inhibit sodium absorption, restore chloride conductance and rehydrate the CF airway surface. In addition, P2Y(2) receptor agonists have been shown to enhance ciliary beat frequency and increase mucociliary clearance in animals and subjects with impaired mucociliary clearance. The normalization of airway surface liquid and enhancement of lung clearance is expected to provide a clinical benefit to CF patients. A number of P2Y(2) agonist compounds have been evaluated in healthy subjects and patients with CF. Most recently, INS37217, a metabolically stable and potent P2Y(2) agonist has been developed and studies have shown it to be well-tolerated when given via inhalation. This compound is currently being evaluated in children and adults with CF lung disease.

Section Reviews: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthnlis: Pharmacological approaches to correct the bioelectric deficits in cystic fibrosis

Despite recent progress in determining the genetic basis of cystic fibrosis (CF), treatment of this disease is almost entirely based on antibiotic therapy to treat lung infections arising from viscous mucous and impaired mucociliary clearance. No treatments are presently available that address the underlying defect created by mutation of the cystic fibrosis transmembrane regulator (CFTR) protein. However, there is currently a great deal of interest in correcting this defect by gene therapy (ineffective at present) and by correcting the erroneous processing of CFTR present with some mutations (early research). In addition, pharmacological treatments aimed at correcting the underlying defect produced by the absence of the CFTR chloride channel are currently under investigation. Pharmacological treatments aimed at the epithelial sodium channel and the alternative chloride channel are the focus of current research reviewed in this article.