Nasal Spray Could Deliver Gene Therapy for Longer, Healthier Lives

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A team of scientists report that they have taken a step toward developing a nasal spray or injection that could one day safely deliver a gene therapy aimed at slowing — or even reversing —  issues related to aging in people. The study was performed on mice and detailed in the journal PNAS.

Led by two pioneering longevity researchers — George Church, synthetic biology lead at the Wyss Institute and Elizabeth Parrish, CEO of BioViva — the team reports that exogenous telomerase reverse transcriptase and follistatin genes were safely and effectively delivered to the mice.  This treatment, then, significantly improved biomarkers associated with healthy aging, boosting mouse lifespan by up to 41% without an increased risk of cancer. The specific biomarkers of aging included improved glucose tolerance, physical performance, as well as preventing body mass loss and alopecia.

In previous studies, scientists showed that the adeno-associated virus — AAV — vector induced overexpression of certain proteins, which can suppress or reverse the effects of aging in animal models. In this study, the team investigated whether the high-capacity cytomegalovirus vector  — or CMV– could be used as an effective and safe gene delivery method for two specific protective factors: telomerase reverse transcriptase — TERT — and follistatin.

Telomere measurements are often used by scientists as an aging biomarker. Usually, short telomeres, which are caps at the end of cells that keep chromosomes from fraying or sticking together, are signs of advanced aging and higher risk for aging-related diseases.  In this case, however, the researchers report that TERT ameliorated the telomere shortening associated with aging and both TERT and follistatin halted mitochondrial structure deterioration.

Telomere lengths have also been associated with cancer. In some cases, researchers see a connection between long telomere lengths and cancer, while other studies point to an increased risk of short telomeres and cancer. Critically, in this study, the scientists found no association between the treatment and increased risk of cancer.

More work is needed, but the scientists suggest that the ultimate goal is to see if the treatment holds in humans.

The researchers write: “Intranasal and injectable preparations performed equally well in safely and efficiently delivering gene therapy to multiple organs, with long-lasting benefits and without carcinogenicity or unwanted side effects. Translating this research to humans could have significant benefits associated with quality of life and an increased health span.”

As the world’s population grows older, age-associated illnesses threaten to overwhelm healthcare systems. Longevity treatments, like this gene therapy, could be a significant help in reducing that burden.

“The impact of this research on an aging population cannot be understated as the global aging-related noncommunicable disease burden quickly rises,” the researchers write.

Church and Parrish also worked with Dabbu Kumar Jaijyan, Anca Selariu, Ruth Cruz-Cosme, Mingming Tong, Shaomin Yang, Alketa Stefa, David Kekich, Junichi Sadoshima, Utz Herbig, Qiyi Tang and Hua Zhu.