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Researchers cure lung fibrosis in mice by lengthening telomeres.

Idiopathic pulmonary fibrosis is a potentially lethal disease associated with the presence of critically short telomeres, and currently lacking effective treatment.  Now, a study from researchers at CNIO cures this disease in mice using a gene therapy capable of lengthening the telomeres, constituting a proof of concept where telomerase activation represents an effective treatment against pulmonary fibrosis.  The team states given the fact telomere shortening is also an indicator of an organism aging, this is the first time pulmonary fibrosis has been treated as an age-related disease by rejuvenating the affected tissues.  The study is published in the journal eLife.

Previous studies have established that telomeres are located at the ends of each chromosome to protect the integrity of the chromosome when the cell divides.  However, telomeres only fulfill their protective function if they are long enough when they shorten too much the damaged cells cease to divide preventing tissue regeneration. Short telomeres are associated with aging and several other diseases, including pulmonary fibrosis, a disease known to affect around 8,000 people in Spain.  The only approved treatments for pulmonary fibrosis to date have no curative effects, as they target the symptoms and not the cause of fibrosis.  The current study develops a therapy based on correcting the molecular cause of pulmonary fibrosis in patients with short telomeres via the introduction of an enzyme called telomerase into the cells of damaged lung tissue to lengthen telomeres.

Their current study shows in a mouse model of lung fibrosis activating the telomerase enzyme to lengthen the telomeres in the lung tissue may constitute an effective therapeutic strategy to treat human pulmonary fibrosis.  Results show only three weeks after treatment the sick animals showed improved lung function and less inflammation and fibrosis; two months after the treatment, the fibrosis had improved or disappeared.

The team states the treatment consists of introducing the telomerase gene into the lung cells using gene therapy. The group first modified a virus to incorporate the telomerase gene and then inject the vectors into the animals.  Data findings show the telomerase gene therapy reverses the fibrotic process in mice, suggesting it could be effective in human patients, opening a new therapeutic opportunity towards the treatment of this disease.

The team surmises their study provides a proof-of-principle telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres.  For the future, the researchers state they have obtained positive results in the treatment of heart infarct, aplastic anemia, and, now, pulmonary fibrosis, with research to bring the therapy to the clinic already underway.

Source: Spanish National Cancer Research Centre (CNIO)

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