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Gene Therapy

Human Gene Therapy Successfully Lengthens Telomeres

Posted on 23 April 2016

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Credit: Reinhard Stindl via Wikimedia Commons

Credit: Reinhard Stindl via Wikimedia Commons

In a bold and courageous move Elizabeth Parrish, CEO of Bioviva USA inc. became the first human to be treated with two gene therapies that her company has developed, one to lengthen her telomeres and one to prevent aging-related loss in muscle mass. With this move, she follows the footsteps of other courageous scientists, such as Nobel laureate Barry Marshall, who used themselves as guinea pigs to prove their discoveries.  

The importance of telomeres

In 2013 a team of renowned scientists drafted a list of nine hallmarks of aging. The team believes that the evidence is sufficiently strong to classify these nine changes as the causes of biological aging. Telomere shortening was one of these nine hallmarks. Telomeres are sequences that cap the ends of the chromosomes and prevent the cell from misidentifying the ends of chromosomes as double strand breaks. If the ends of chromosomes are misidentified as a double strand break, then the cell would fuse two chromosomes together which can lead to cancer or in the best case scenario the death of that individual cell. As we age the length of these protective sequences shorten and may eventually reach a critical size leading to one of three outcomes: (i) cell death, (ii) cell senescence, or (iii) genomic instability. Senescent cells are cells that have undergone a terminal growth arrest but remain viable. However, these senescent cells may contribute to aging by secreting molecules that cause harmful systemic effects such as inflammation.  

Building on animal research

The Blasco lab developed adeno-associated viral gene therapy with telomerase, the enzyme that lengthens telomeres, and tested it in mice. In 2012 they published their findings in EMBO Molecular Medicine and showed that mice treated with telomerase gene therapy at 1 year of age had a 24% increase in mean and 13% increase in maximum lifespan. Importantly, the Blasco lab did not find an increased risk of cancer in the gene therapy treated mice, an often voiced concern with this type of therapy. 

Elizabeth Parrish, CEO of Bioviva USA inc.  

Elizabeth Parrish, CEO of Bioviva USA inc.  

The Texas-based company SpectraCell measured the telomere length in the leukocytes of Miss Parrish before and half a year after the gene therapy. The results show that the average telomere length has increased from 6.71kb to 7.33kb (an increase of 9%). 

The first steps

The results are promising but are currently just a proof of principle. These results will need to be replicated in a trial with more than a single subject and telomere length in other tissues will need to be investigated. A limitation for this last question is that few human tissues can safely be sampled (blood and skin are the two most easily sampled tissues). The scientists will also have to evaluate not just if the treatment extends telomeres but also what effect it has on other physiological parameters. For example, TA Sciences is marketing an oral telomere lengthening pill that in human tests conducted by the company has been found to lower fasting blood glucose, blood pressure, LDL, increase bone mineral density in the spine, and has shown protective effects in patients suffering from macular degeneration. We look forward to see if Bioviva’s gene therapy causes similar physiological changes. Finally, we should note that another company, Telocyte, is also working on clinical trials with telomerase gene therapy as a potential treatment for Alzheimer’s disease.
Source: Eurekalert

Contributor: Sven Bulterijs

Nakamura AJ et al. (2009). Telomere-dependent and telomere-independent origins of endogenous DNA damage in tumor cells. Aging 1(2): 212–218.

Bernardes de Jesus B et al. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med 4(8): 691-704.

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