Treatment of Pulmonary Symptoms of Cystic Fibrosis with Cholecalciferol

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Researchers
Gill Diamond
Kristina DiFranco
Scott Randell
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John Byatt
Assistant Director 352-392-8929

Treatment with Inhaled Cholecalciferol Promises to Improve Lung Function in Patients with the Most Common Form of Cystic Fibrosis

This topical vitamin D treatment for pulmonary symptoms of Cystic Fibrosis promises to improve lung function in patients with the most common form of the disease. Cystic Fibrosis affects more than 28,000 individuals in the United States alone and dramatically reduces average lifespan and quality of life of affected individuals. Cystic Fibrosis is a genetic disease that affects mucosal membranes of the body with serious effects on the lungs, making it difficult for victims to breathe and making them more susceptible to infection. The clinical symptoms of Cystic Fibrosis are due to mutations in a protein, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is normally expressed in cells in the lungs, pancreas and a number of other organs. More than 100 different mutations in the CFTR gene can lead to Cystic Fibrosis, but the most common mutation (delta F508) accounts for about 75 percent of all cases. None of the drug treatments available effectively treat the pulmonary symptoms of Cystic Fibrosis. However, researchers at the University of Florida have discovered that topical application of cholecalciferol (the “inactive” form of vitamin D) results in increased CFTR protein expression by lung cells and less viscous mucus production by these cells. This discovery suggests that an inhaled formulation of cholecalciferol can be developed that will provide an effective treatment for the pulmonary symptoms of Cystic Fibrosis.

Application

Treatment of the pulmonary symptoms of Cystic Fibrosis with vitamin D

Advantages

  • Low cost of cholecalciferol and vitamin D, reducing drug manufacturing costs
  • Treatment via an inhaler, providing an effective and easily administered solution accessible to both children and adults
  • Low toxicity of cholecalciferol and vitamin D, offering therapy with a wide therapeutic index and little risk of harmful side effects for patients
  • May decrease necessity for supplemental treatments, such as antibiotics for lung infections, thereby reducing overall treatment costs, providing large market advantage

Technology

Cholecalciferol is generally accepted as being converted to the active form of Vitamin D by a two-step process occurring in the kidneys and liver; however, researchers at the University of Florida now have shown that the epithelial tissue of the lungs has the capacity to convert cholecalciferol into calcidiol, which is then converted to calcitriol, the active form of vitamin D. Furthermore, the researchers have demonstrated that lung epithelial cells, with the delta F508 CFTR mutation, exposed to cholecalciferol will stimulate greater expression of CFTR protein on the cell surface. It’s thought that the delta F508 mutation disrupts processing of CFTR protein, resulting in little to no cell surface expression and resulting in reduced ion transport and abnormal mucus production. Treatment with cholecalciferol appears to stimulate more normal CFTR protein processing so that more of this vital protein is expressed on the surface of lung epithelial cells. Thus, either cholecalciferol or vitamin D could be administered to the lung epithelial cells of the lungs via an aerosol and thereby improve lung function.