hTERT Gene Therapy and Telomere Health: Hope for Alzheimer’s and Other Dementias?
Dementia is closely linked to the aging process. It robs people of their cognitive functioning, memories and, ultimately, their very sense of self. Countless studies have been conducted to get to the bottom of things. One finding has come up again and again: telomere attrition is directly implicated with the onset and progression of neurodegenerative diseases like Alzheimer’s. (Honig, 2012)
Telomere attrition predicts mortality and the development of aging-related health conditions. This is true for patients with inherited telomere syndrome, as well as the general population. For this reason, the length of telomeres are a major focal point for dementia research. (Blackburn, 2015)
Telomeres, located at the ends of chromosomes, are repetitive sequences of DNA that serve to protect us from chromosomal damage. Because the ends of DNA are incapable of being copied, telomeres shorten after every cell division. This phenomenon induces a damage response, eventually culminating in cellular death. (Martinez, 2018)
The rate of telomere attrition is influenced by genetic factors as well as environmental ones. Outside of chronological age, predictive factors like smoking and diabetes can negatively impact telomere length (Nawrot, 2010), (Salpea, 2010). Another culprit is inactivity. A sedentary lifestyle is shown to increase the aging process including telomere attrition (Cherkas, 2008).
In a large-scale, multiethnic, community based study of aging and dementia, nearly two thousand subjects over 65 were observed to identify a relationship between the progression of dementia and telomere length. Their findings suggest subjects who passed away during follow-up had shorter telomere lengths compared to surviving participants. Moreover, those who developed dementia had markedly shorter telomeres. Shorter telomeres were also associated with early onset dementia (Honig, 2012).
Indeed, telomere attrition has for years been implicated in cognitive impairment, hyperphosphorylation of tau, and amyloid accumulation, all telltale signs for development of dementia and Alzheimer’s disease (Zhang, 2003).
Although dementia has been long considered irreversible and treatments limited, induction of telomerase through gene therapy has yielded remarkable results. One study on an animal model of neurodegeneration led to the observation that telomerase induction decreased DNA damage in the brain, increasing neurogenesis while decreasing neuroinflammation (Whittemore, 2019).
A human dementia study analyzed by BioViva was published in The Journal of Regenerative Biology and Medicine in November. It revealed the proprietary dual gene therapy resulted in increased telomere length in dementia patients. This increase was correlated with mitigation of brain degeneration in MRI tests, and an improvement on the Folstein exam, a standard exam for gauging cognitive impairment in dementia patients.
To illustrate the staggering success of a treatment leading to improved scores, it is important to note that no previous treatment in all of the literature on dementia has recorded an improvement on the Folstein test, which measures decline in cognitive tasks. Dementia is harrowing, but we now have hope.
References and Works Cited
Honig LS, Kang MS, Schupf N, Lee JH, Mayeux R. Association of Shorter Leukocyte Telomere Repeat Length With Dementia and Mortality. Arch Neurol. 2012;69(10):1332–1339. doi:10.1001/archneurol.2012.1541
Blackburn, Elizabeth H., Elissa S. Epel, and Jue Lin. “Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection.” Science 350.6265 (2015): 1193–1198.
Martínez, Paula, and Maria A. Blasco. “Heart-breaking telomeres.” Circulation research 123.7 (2018): 787–802.
Fani L, Hilal S, Sedaghat S, et al. Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study. J Alzheimers Dis. 2020;73(2):707–714. doi:10.3233/JAD-190759
Nawrot TS, Staessen JA, Holvoet P, et al. Telomere length and its associations with oxidized-LDL, carotid artery distensibility and smoking. Front Biosci (Elite Ed). 2010;2:1164–116820515788
Salpea KD, Talmud PJ, Cooper JA, et al. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis. 2010;209(1):42–5019889414
Cherkas LF, Hunkin JL, Kato BS, et al. The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length. Arch Intern Med. 2008;168(2):154–158. doi:10.1001/archinternmed.2007.39
Zhang, Jianmin, et al. “Telomere dysfunction of lymphocytes in patients with Alzheimer disease.” Cognitive and Behavioral Neurology 16.3 (2003): 170–176.
Whittemore K, Derevyanko A, Martinez P, et al. Telomerase gene therapy ameliorates the effects of neurodegeneration associated to short telomeres in mice. Aging (Albany NY). 2019;11(10):2916–2948. doi:10.18632/aging.101982
Authored by Ryan Hall
While in Michigan, he also trained as an athlete at the United States Olympic Education Center, where he achieved the status of a multiple-time University All-American in Greco-Roman wrestling. He has authored several plays and a collection of poetry. Some of his major areas of interests includes: Finance, Literature, and Religious Studies.
Ryan is available to contact via email at: arete.aphthiton@gmail.com
