Primary ciliary dyskinesia: prospects for new therapies, building on the experience in cystic fibrosis.
Primary ciliary dyskinesia (PCD) is a genetic disease associated with abnormal ciliary structure and function, leading to impaired mucociliary clearance, an important primary innate defense mechanism that protects the lungs. Drugs that can effectively treat PCD should overcome the defect in ciliary function and increase the mucociliary clearance. However, there are currently no therapeutic strategies that correct the inborn error of ciliary dysfunction to restore mucociliary clearance. It is unclear if osmolar agents like hypertonic saline or mannitol, therapies that increase the respiratory surface hydration like ion-channel regulators, or therapies aimed at reducing inflammation or mucus production, or softening the mucus will be effective in PCD. Many of these modalities are used in cystic fibrosis, yet no evidence exists to support their routine use in PCD. Newer genetic modifiers show an exciting potential for personalized medication, combining selection of patients with a common genetic mutation and a drug treatment that has been specifically designed to overcome that mutation, and will greatly enhance the therapeutic arsenal for PCD. This review summarizes current and future prospects for these therapeutic options.
Amirav
Israel
I
Department of Pediatrics, Ziv Medical Center, Safed, Technion, Haifa, Israel.
Cohen-Cymberknoh
Malena
M
Shoseyov
David
D
Kerem
Eitan
E
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D004234:Diuretics, Osmotic / Q000627:therapeutic use*; D005100:Expectorants / Q000627:therapeutic use*; D006801:Humans; D006982:Hypertonic Solutions / Q000627:therapeutic use*; D007619:Kartagener Syndrome / Q000188:drug therapy* / Q000235:genetics; D009079:Mucociliary Clearance / Q000187:drug effects; D009154:Mutation / Q000187:drug effects; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D004234:Diuretics, Osmotic; D005100:Expectorants; D006982:Hypertonic Solutions; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I