Question

Understanding the molecular consequences of CFTR mutations has
significantly contributed to the development of new treatments for
cystic fibrosis.
(a) Discuss how mutations in CFTR lead to cystic fibrosis lung disease
(b) Describe examples of at least three novel treatments that have
been or are being developed to treat cystic fibrosis
(total min 500words)

Answer 1

Cystic fibrosis is a genetic disorder which mostly affects the lung and also pancreas, liver intestine and kidney. It is inherited in an autosomal recessive manner. It causes mutation in both the copies of the gene for the cftr protein. Those with single copies are just the carrier. The most common mutation is deltaf508 is a deletion of 3 nucleotide that results in the loss of amino acid phenylalanine at the 508yh position on the protein. This mutation accounts for 2/3 of cystic fibrosis cases. It creates a protein that does not fold normally and is not appropriatrly transported to the cell membrane, resulting in its degradation. Other mutation results in protein that are too short because production is ended prematurely.

Gene therapy is said to be the novel method for the treatment of cystic fibrosis. It involves the transfer of correct copies of cftr DNA to the epithelial cells in the airways.

Convential pulmonary treatment of CF has targeted the downstream consequences of the disease namely mucous plugging and infection. Physiotherapy to aid clearence of airway secretions is one of the mainstays for the treatment of CF. It uses positive expiratory devise which uses antibiotics.

Various pharmacological agents are available to enhance the expression of CFTR protein. CFTR modulator are specific molecules targeted towards select CFTR defect, promoting full expression and functionality. Modulator includes read through agents, corrector and potentiator.

Read through agents include aminoglycosides