title: Role of magnesium in the failure of rhDNase therapy in patients with cystic fibrosis.
abstract: BACKGROUND
  In the management of cystic fibrosis (CF), rhDNase-I inhalation is widely used to facilitate the removal of the highly viscous and elastic mucus (often called sputum) from the lungs. However, an important group of CF patients does not benefit from rhDNase-I treatment. A study was undertaken to elucidate the reason for the failure of rhDNase-I in these patients and to evaluate strategies to overcome this.
  
  
  METHODS
  The biochemical properties, physical properties, and degradation by rhDNase-I of sputum obtained from clinical responders and non-responders to rhDNase-I were compared, and the ability of magnesium to reactivate rhDNase-I in DNA solutions and in sputum was investigated. The effect of oral magnesium supplements on magnesium levels in the sputum of patients with CF was also examined.
  
  
  RESULTS
  Sputum from clinical responders was extensively degraded in vitro on incubation with rhDNase-I, while sputum from clinical non-responders was not degraded: the median decrease in sputum elasticity in the two groups was 32% and 5%, respectively. Sputum from clinical responders contained significantly higher concentrations of magnesium than sputum from non-responders (2.0 mM v 1.3 mM; p = 0.020). Sputum that could not be degraded by rhDNase-I became degradable after preincubation with magnesium. The effect of magnesium on rhDNase-I activity was mediated through actin. Oral intake of magnesium enhanced the magnesium concentration in the sputum of CF patients.
  
  
  CONCLUSIONS
  Increasing the magnesium concentration in sputum by, for example, oral magnesium supplements may be a promising new strategy to overcome the failure of rhDNase-I in patients with CF.
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. niek.sanders@ugent.be
authors.forename: N N
authors.initials: NN
authors.lastname: Sanders
authors.forename: H
authors.initials: H
authors.lastname: Franckx
authors.forename: K
authors.initials: K
authors.lastname: De Boeck
authors.forename: J
authors.initials: J
authors.lastname: Haustraete
authors.forename: S C
authors.initials: SC
authors.lastname: De Smedt
authors.forename: J
authors.initials: J
authors.lastname: Demeester
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage* / Q000032:analysis; D008297:Male; D011188:Potassium / Q000032:analysis; D013183:Sputum / Q000737:chemistry / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D008274:Magnesium; D011188:Potassium