Gene therapy vectors carrying the telomerase gene do not increase the risk of cancer

Gene therapy with telomerase was developed by CNIO in 2012 and has proved effective in mice against infarction, as well as in mouse models of aplastic anaemia and idiopathic pulmonary fibrosis associated to short telomeres


Negative results and findings in science are perhaps less newsworthy, but they are no less important. Particularly when, as in this case, they demonstrate that a possible new therapeutic pathway against idiopathic pulmonary fibrosis and other diseases associated to short telomeres is in fact safe. Researchers from the Spanish National Cancer Research Centre (CNIO) have shown in a new study that the gene therapy with telomerase that they have developed, and which has proven to be effective in mice against diseases caused by excessive telomere shortening and ageing, does not cause cancer or increase the risk of developing it, even in a cancer-prone setting.

This paper has been published in the journal PLoS Genetics with the participation of Miguel Angel Muñoz and Paula Martinez from the Telomeres and Telomerase Group led by Maria A. Blasco at the CNIO. In this study, CNIO researchers also collaborated with by Fàtima Bosch from the Gene Therapy Centre (CBATEG) at Barcelona's Autonomous University.

CNIO's Telomeres and Telomerase Group has for years now been investigating the possibility of using the enzyme telomerase to treat pathological processes related with telomere shortening, as well as diseases associated with ageing - cardiovascular and neurodegenerative diseases, among others - and even the ageing process itself. In 2012, they designed a highly innovative strategy: a gene therapy that reactivates the telomerase gene using adeno-associated viruses (AAV). These gene therapy vectors do not integrate in the genome of the host cell, thus telomerase only performs its telomere-reparative actions during a few cell divisions before the vector is diluted out. In this manner, a potential risk associated with the activation of telomerase, such as promoting cancer, it is minimized. But to what extent? The potential medical use of telomerase still clashes with fears surrounding a possible increased risk of cancer.

The paper being published now specifically tackles this question by applying gene therapy to an animal model, a mouse, which reproduces human lung cancer and which, therefore, already has a greater risk of developing this disease. The results are negative: "The activation of telomerase by means of [this gene therapy] does not increase the risk of developing cancer", not even in these mice, where tumours are forced to appear in a relatively short time, write the authors.

"These findings suggests that gene therapy with telomerase appears to be safe, even in a pro-tumour context", noted Blasco. "In our research, we were already seeing that this gene therapy does not increase the risk of cancer, but we wanted to conduct what is known as a 'killer experiment', an experiment that creates the worst conditions for your hypothesis to hold true; if it survives even under those circumstances, the hypothesis is truly solid. That is why we chose these mice; they are animals that spontaneously develop a type of lung cancer that is very similar to the human form, which normally never appears in normal mice. We can't think of any other experiment that would provide a better demonstration of the safety of this therapy".

How to use a double-edged sword