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 which lengthens the telomeres, constituting a proof of concept that telomerase activation represents an effective treatment against pulmonary fibrosis. The team state given that telomere shortening is also an indicator of an organism ageing, this is the first time that 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 show 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 ageing and with several diseases such as pulmonary fibrosis, which affects around 8,000 people in Spain, is one of them. 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 which is based on correcting the molecular cause of pulmonary fibrosis in patients with short telomeres, by introducing an enzyme called telomerase into the cells of damaged lung tissue to lengthen telomeres.
Their current study shows that in mice modelling 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 that 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 state that the treatment consists of introducing the telomerase gene into the lung cells using gene therapy. The group first modify 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, which suggests that it could be effective in human patients, opening a new therapeutic opportunity towards the treatment of this disease.
The team surmise their study provides a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres. For the future, the researchers state that they have obtained positive results in the treatment of heart infarct, aplastic anemia and, now, pulmonary fibrosis; in the case of heart infarct, research to bring the therapy to the clinic is already underway.