Results from a French clinical trial published in BMC Medicine show how a small percentage of CF sufferers with a rare genetic stop mutation responded positively to gentamicin treatment.

Aleksander Edelman and Isabelle Sermet-Gaudelus of Faculty de Medicine Necker in Paris led collaborators from several French institutions studying how the antibiotic gentamicin affected CF patients with a stop mutation. The team used a dual reporter gene assay first in vitro and then in CF patients. The study found that a small subgroup of patients with the Y122X mutation, found mainly in inhabitants of Reunion island, responded to gentamicin treatment.

Cystic fibrosis is caused by mutations in the gene that encodes the Cystic Fibrosis Transmemrane Conductance Regulator (CFTR) protein. Over 1500 mutations have been described since this gene's discovery. Premature stop mutations, which includeY122X, are found in around 10% of CF patients. Gentamicin reversed stop codons in the Y122X gene, and helped restore the CFTR protein, improving patients' respiration.

Gentamicin itself may not be an ideal drug option, as it may cause serious side effects for some patients, including ear and kidney damage. The authors suggest that other drugs, such as amikacin or PTC124, with a comparable mode of action and fewer side effects, may have treatment potential. The in vitro method used to predict the trial's outcome could be a first step to developing treatments effective for patients with CF and other diseases where premature stop codons play a role.

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Gene tests are currently not available for IPF, but scientists are evaluating ways to assess risk of disease by screening telomere length.

"If we follow the genetic threads of families that inherit IPF, it may lead us to understand the genetic properties causing more common forms of the disease," says Armanios.

Patients with non-inherited IPF also may have short telomeres, so, says Armanios, "there may be other causes for short telomeres, such as older age and smoking, which also happen to be the main risk factors for IPF."

To determine the link between short telomeres and non-inherited IPF, investigators will need to study a larger group of these patients.

If studies reveal a solid link between the two, Armanios says that it may change the way IPF is treated.

"For many years, we've thought that IPF is caused by an immune attack against the lungs, even though current therapies aimed at dampening the immune system don't work," she explains. "If we?re not so tied to immune suppression therapies, we could eventually tailor drugs to a different target."

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