Enzyme-related Gene Therapy May Be Way to Treat Pulmonary Fibrosis, Study Shows

Enzyme-related Gene Therapy May Be Way to Treat Pulmonary Fibrosis, Study Shows

A gene therapy revolving around a chromosome-protecting enzyme could be a way to treat pulmonary fibrosis, Spanish researchers report.

Proper levels of the enzyme, telomerase, are necessary to generate the right form of a protein that protects chromosomes when a cell divides. The proteins, telomeres, lie on the end of chromosomes. They function only if they are of a certain length. If they’re too short, cells stop dividing.

Increasing levels of the enzyme leads to telomeres that are long enough to function, researchers said.

Their study, “Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres,” was published in the journal eLIFE.

Generally, shorter telomeres are associated with aging. But they are also associated with pulmonary fibrosis and other diseases.

A team at the Spanish National Cancer Research Center wondered if they could restore telomeres’ function in a mouse model of pulmonary fibrosis. They used a gene therapy called AAV9 that targets lung cells involved in tissue regeneration. Scientists dub them alveolar type II cells, or ATIIs.

A key finding of the study was that one to three weeks of the therapy improved the mice’s lung function and decreased their inflammation and tissue scarring, or fibrosis. After eight weeks of the treatment, the mice had fewer fibrotic lesions, or none at all.

In addition, the treatment led to longer telomeres, more ATII cell growth, and less DNA damage and cell death, according to the researchers, who are with the center’s Telomere and Telomerase Group.

An analysis of the ATII cells’ gene activity showed that the treatment led to less activity in fibrosis and inflammation pathways.

“We provide a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres,” the researchers wrote.

“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,” Juan Manuel Povedano, a co-first author of the paper, said in a press release.

Unlike gene therapies that target a disease’s symptoms, this one is exciting because it targets a disorder’s underlying cause, the researchers said.

“The most relevant aspect of our work is that it suggests a potentially viable and effective solution to a real clinical problem, pulmonary fibrosis, for which there is still no treatment,” said Paula Martínez, the other co-first author. “Our therapy is based on correcting the molecular cause of pulmonary fibrosis in patients with short telomeres, introducing into the cells of damaged lung tissue the only enzyme capable of lengthening telomeres, telomerase.”

“The strategy devised by the CNIO [cancer center] group is very encouraging,” said Fàtima Bosch, a gene therapy expert at the Autonomous University of Barcelona. “Although we are still far from reaching the clinic [clinical trials], we are already generating gene therapy vectors for human therapy.”


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