Researchers at the University of Iowa Carver College of Medicine recently reported that the FDA-approved drug tromethamine may offer therapeutic benefits for patients with cystic fibrosis (CF). The findings were described in the study “Repurposing tromethamine as inhaled therapy to treat CF airway disease,” published in the journal JCI Insight.
Cystic fibrosis is a genetic condition in which the lungs and digestive system become clogged with thick sticky mucus. Symptoms usually start in early childhood and include persistent cough, recurring chest and lung infections, and poor weight gain.
Cystic fibrosis is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). Those with a single working copy are carriers, and otherwise mostly normal. The CFTR protein is involved in the production of sweat, digestive fluids, and mucus. In cystic fibrosis, loss of the CFTR anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses.
One potential therapeutic approach to raise ASL pH is to aerosolize pH buffers. A clinical trial assessing aerosolized HCO3 in patients with cystic fibrosis is currently ongoing.
Tromethamine (Tham or tris[hydroxymethyl]aminomethane acetate) is an FDA-approved buffer in clinical use. It affects the balance of water and electrolytes in the body. The drug is used as a treatment for metabolic acidosis (an electrolyte imbalance). Tromethamine is known to alkalinize serum with an effect that persists for 16 to 48 hours.
The team of researchers found that inhaling aerosolized tromethamine raised ASL pH in both pigs and CF patients. Researchers also found that tromethamine, either alone or in combination with hypertonic saline (a salt-water solution that contains a greater concentration of salt than normal saline, and therefore a greater concentration of salt than our body fluids), increased the pH level.
The results also showed that treatment with tromethamine improved bacterial death in the airways of pigs with cystic fibrosis, as well as in sputum samples in humans with cystic fibrosis.
Based on the results, the research team concluded that tromethamine either alone or in combination with hypertonic saline might be of therapeutic benefit in cystic fibrosis airway disease.