It Takes Two to Treat Cystic Fibrosis

Treating delta508 mutation and domain-domain interaction simultaneously may improve cystic fibrosis treatment

(RxWiki News) Treating cystic fibrosis may be a two-fold problem according to researchers. A new study highlights two cellular defects which could lead to improved cystic fibrosis treatment.

Researchers discovered two cellular defects found within the cystic fibrosis mutation. Cystic fibrosis is a genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), which is a protein. Within the CFTR, a deleted amino acid causes improper folding of the CFTR and also causes binding domain instability. Targeting these two defects could lead to better cystic fibrosis treatments.

"Ask your doctor about current cystic fibrosis treatments. "

The cystic fibrosis study was led by Gergely Lukacs, M.D., Ph.D., from McGill University Faculty of Medicine's Department of Physiology. Researchers developed computer models of CFTR to examine the most common cause of cystic fibrosis, the deltaF508 mutation. DeltaF508 is the deletion of an amino acid within CFTR which causes cystic fibrosis.

The CFTR protein regulates how a cell transports ions or water across its surface. A mutation within CFTR, deltaF508, causes improper chloride transportation, creating a buildup of thick mucus in the lungs. Cystic fibrosis occurs when a person has two defective CFTR cells, one from their mother and one from their father.

CFTR is made up of five different nucleotide binding sites. Nucleotides combine to form CFTR and deltaF508 is found in the first nucleotide binding site (NB1). DeltaF508 causes an improperly folded CFTR cell causing structural issues that prevents the regulation of chloride.

While deltaF508 occurs at NB1, researchers discovered that deltaF508 creates weakens the second nucleotide binding site (NB2). In order to correct the improper folding of CFTR and restore the normal function of CFTR, Dr. Lukacs believes treatments need to target deltaF508 as well as the “domain-domain interaction” between NB1 and NB2.

Researchers concluded that both issues, deltaF508 and the domain-domain interaction, need to be treated at the same time in order to restore the normal function of the cell. Dr. Lukacs believes the reason why current treatments in development are not that effective in treating cystic fibrosis is because the treatment only targets one problem, not both.

Future studies can look at deltaF508 and domain-domain interaction within humans and identify possible ways to treat both defects associated with cystic fibrosis. Targeting both defects could lead to better cystic fibrosis treatments

The study was funded by grants from The Cystic Fibrosis Foundation, Cystic Fibrosis Canada, The Canadian Institutes for Health Research, Canada Research Chair program and the Canada Foundation for Innovation.

This study was published in the January edition of Cell.

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Review Date: 
March 13, 2012