Early therapy of cystic fibrosis (CF)

At present only the symptoms of the hereditary disease CF, which results in death at a young age, are being treated, not the actual cause. The novel preventive therapeutic strategy consists of an early treatment of CF before any disease-specific symptoms can be detected. In animal trials the early therapy with sodium channel blocker amiloride, commencing immediately after birth, prevents the development of CF. Further supporting data from a study with 50 infants using hypertonic sodium chloride are already available.
Further clinical testing of the invention-based therapy is already being planned - patents have been granted, project partners are being sought!

Cystic Fibrosis (CF) is an inherited, non-curable and life-limiting autosomal recessive metabolic disease of the lung. Other organs can also be affected, e.g. pancreas, intestine and gall bladder.
Over 5 % of the European population is carriers of the CF mutation; worldwide there are some 60,000 people suffering from CF. Between 300 and 400 babies with the disease are born each year in Germany alone.

At present, only the symptoms of CF are being treated, not the actual cause. Physical therapies in combination with mucus solvents help patients to remove mucus from the lung. Antibiotics are used against bacterial infections of the lung. Life expectancy under current therapeutic conditions is around 40 years.

Neonatal screening for CF
The earlier the CF diagnosis occurs, the earlier treatment can commence and the better are the chances of the patient. Following this principle, the Cystic Fibrosis Center at the Heidelberg University Clinic under the leadership of Professor Marcus Mall has successfully applied a new, simple and safe biochemical CF-test (Sommerburg et al., JIMD, 2010) and is actively campaigning in support of a regular neonatal screening program for the early detection of metabolic diseases.

Innovative therapy for CF
In parallel with the development of the screening test, Professor Mall and his team developed a novel preventive therapeutic strategy (Zhou et al., AJRCCM, 2008) for the early treatment of CF before any disease-specific symptoms can be detected. The early therapy with amiloride commencing during the first days after birth prevents the development of CF in animal trials.

Results of the innovative CF therapy
In animal trials, transgenic CF-mice (Mall et al., Nat. Med., 2004) were treated successfully with amiloride via nasal application, provided they were treated prior to CF-symptoms developing, i.e. immediately following birth (Zhou et al., AJRCCM, 2008).
In addition, the early amiloride therapy positively affects the mucus membrane and the formation of mucus (Figure 2) as well as the goblet cell metaplasia, the chronic inflammation and the formation of lung emphysema. These results demonstrate that the preventive treatment with amiloride can be an effective therapy for CF.

• Early treatment with sodium channel blocker amiloride immediatley following birth:
  • reduces the thick mucus in the lung, improves respiration, reduces lung infections and prolongs survival,
  • because the accelerated salt and water absorption in the airway is effectively suppressed
• Simplified registration requirements due to the orphan disease status
• Tested active substance with novel application

Preventive therapy of cystic fibrosis (CF).