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Study Shows Telomerase Gene Therapy Does Not Increase Cancer Risk – Article by Steve Hill

Study Shows Telomerase Gene Therapy Does Not Increase Cancer Risk – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on August 27, 2018. This article takes another step forward toward clearing up a common misconception that many scientists and laypeople hold, i.e., the notion that extending telomeres causes cancer. Mr. Hill cited a recent article published in the journal PLOS Genetics, in which researchers found there to be no increase in cancer, even when telomeres were extended in mice from cancer-prone mouse strains. Hopefully this article will help researchers reevaluate this misconception so this very important age-reversal research will be advanced much faster.

~ Bobby Ridge, Assistant Editor, June 20, 2019

Researchers have demonstrated that telomerase gene therapy does not increase the risk of cancer, even in strains of mice that are particularly susceptible to cancer [1].

A tale of telomeres

Short telomeres trigger cellular senescence and are thought to be one of the primary hallmarks of aging, which has led to various researchers seeking ways to restore the telomeres in order to prevent cells from dying and to encourage division and tissue regeneration. We won’t go over the basics of telomeres and how they influence aging  here, but if you would like to learn more, check out our telomeres article, which explains it all.

Ever since Dr. Maria Blasco and her team at the Spanish National Cancer Research Centre (CNIO) first used telomerase gene therapy in mice back in 2012, a debate has raged about the potential of telomerase for regenerating tissue and reversing some aspects of aging versus the risk of it causing cancer.

Despite the concerns, it has proved effective against infarction by spurring regeneration of cardiac tissue and in treating aplastic anaemia and idiopathic pulmonary fibrosis in mice; all of these conditions are associated with critically short telomeres.

The CNIO’s Telomeres and Telomerase Group, which conducted the new study, has been investigating the potential of using telomerase therapy to treat age-related diseases for many years. Its 2012 publication featured a specially developed gene therapy that used an adeno-associated virus (AAV) to deliver a payload to cells that reactivated the telomerase gene, which can restore lost telomeres by creating the telomerase enzyme, and it appeared to delay and reverse certain aspects of aging [2].

Its AAV therapy is special in that the vectors do not integrate into the genomes of the target cells. Therefore, the telomerase activation only lasts for a few cell cycles before its effects cease. This transient activation of telomerase makes for a safety net, as unlimited cell division is only a step away from cancer.

Abstract

Short and dysfunctional telomeres are sufficient to induce a persistent DNA damage response at chromosome ends, which leads to the induction of senescence and/or apoptosis and to various age-related conditions, including a group of diseases known as “telomere syndromes”, which are provoked by extremely short telomeres owing to germline mutations in telomere genes. This opens the possibility of using telomerase activation as a potential therapeutic strategy to rescue short telomeres both in telomere syndromes and in age-related diseases, in this manner maintaining tissue homeostasis and ameliorating these diseases. In the past, we generated adeno-associated viral vectors carrying the telomerase gene (AAV9-Tert) and shown their therapeutic efficacy in mouse models of cardiac infarct, aplastic anemia, and pulmonary fibrosis. Although we did not observe increased cancer incidence as a consequence of Tert overexpression in any of those models, here we set to test the safety of AAV9-mediated Tert overexpression in the context of a cancer prone mouse model, owing to expression of oncogenic K-ras. As control, we also treated mice with AAV9 vectors carrying a catalytically inactive form of Tert, known to inhibit endogenous telomerase activity. We found that overexpression of Tert does not accelerate the onset or progression of lung carcinomas, even when in the setting of a p53-null background. These findings indicate that telomerase activation by using AAV9-mediated Tert gene therapy has no detectable cancer-prone effects in the context of oncogene-induced mouse tumors.

More support for telomerase gene therapy

Despite this safety measure, the medical use of telomerase therapy has been held back due to concerns of cancer risk, so the researchers at CNIO set out to see if this concern is justified.

To do this, they used this gene therapy in a mouse model that is at high risk of lung cancer. Their results showed that activating the telomerase gene via their gene therapy does not increase the risk of developing cancer, not even in this cancer-prone mouse strain.

These findings suggest that this gene therapy appears to be safe even in a pro-cancer environment. The authors chose this cancer-prone mouse strain to create a “killer experiment”, which creates a worst-case scenario that tests a hypothesis to its limit; if the hypothesis holds true despite the extreme scenario, it shows that the hypothesis is good. Because this therapy did not increase cancer risk in this extremely vulnerable mouse population, it demonstrates that telomerase gene therapy is possibly safe enough to use in humans.

The road ahead

The safety and utility of telomerase therapy is becoming more apparent with each passing year. The purpose of this new study was to demonstrate the plausibility of using telomerase to safely treat many diseases that currently have no cure, such as pulmonary fibrosis, and to help speed up its progress into human clinical trials.

Conclusion

The potential of telomerase gene therapy has long been debated amid cancer concerns, but this experiment suggests that those concerns are unfounded. There is no doubt that telomerase can and does regenerate tissue when it is delivered via gene therapy and that it does reverse various aspects of aging in multiple models.

Can we safely use what some people describe as a double-edged sword and apply it the fight against aging? This experiment strongly suggests that yes, we can.

Literature

[1] Muñoz-Lorente, M. A., Martínez, P., Tejera, Á., Whittemore, K., Moisés-Silva, A. C., Bosch, F., & Blasco, M. A. (2018). AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer. PLoS genetics, 14(8), e1007562.

[2] de Jesus, B. B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO molecular medicine, 4(8), 691-704.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Dr. Bill Andrews Interviewed by John Murrieta of the Science-Based Species Channel

Dr. Bill Andrews Interviewed by John Murrieta of the Science-Based Species Channel

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Bill Andrews
John Murrieta


John Murrieta of the channel Science-Based Species interviewed Dr. Bill Andrews, the U.S. Transhumanist Party’s Biotechnology Advisor, in October 2018. Watch this interview on YouTube here.

In this video, Dr. Andrews discusses the research he does at Sierra Sciences with the aim to reverse aging and extend lifespans by extending telomeres, as well as the forthcoming gene-therapy clinical trial by Libella Gene Therapeutics.

This interview with recorded by U.S. Transhumanist Party Secretary Bobby Ridge at the Fifth Enlightenment Salon, hosted by U.S. Transhumanist Party Chairman Gennady Stolyarov II.

Telomere Coin Announcement by Dr. Bill Andrews and the defytime Group

Telomere Coin Announcement by Dr. Bill Andrews and the defytime Group

logo_bgBill Andrews
defytime Group


Editor’s Note: The U.S. Transhumanist Party’s Biotechnology Advisor, Dr. Bill Andrews, provides information regarding an innovative effort to fund his longevity research via the new Telomere Coin cryptocurrency. Dr. Andrews has long pursued the goal of lengthening human telomeres and reversing biological aging. The U.S. Transhumanist Party will provide more information regarding the Telomere Coin as it becomes available. The above video was created by the defytime Group. To find out more about defytime and the Telomere Coin, read the whitepaper here. The U.S. Transhumanist Party considers the Telomere Coin to be an Allied Project and looks forward to the results of this innovative approach in raising much-needed funds for the work of Dr. Andrews. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, May 8, 2018

Message from Dr. Bill Andrews: The Telomere Coin could be the best opportunity ever to get funding for my research.  The Initial Coin Offering (ICO) hasn’t started yet but will in July. But, now there is a pre-sale of the coin underway for investors to buy coins at a lower price. To buy the coins go to http://defytime.group and click “Go to ICO” and then click on “Join Pre-Sale”.

New Clinical Study May Be the World’s First Cure for Alzheimer’s Disease – Press Release from Libella Gene Therapeutics

New Clinical Study May Be the World’s First Cure for Alzheimer’s Disease – Press Release from Libella Gene Therapeutics

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Libella Gene Therapeutics


ORLANDO, Fla.Jan. 10, 2018 /PRNewswire/ — Libella Gene Therapeutics LLC will conduct an OUS (outside the United States) clinical trial in Cartagena, Colombia, using gene therapy to reverse age-related diseases, starting with Alzheimer’s. Unlike traditional drugs, which tend to be taken for months or years at a time, gene therapy interventions are intended to be one-off treatments that tackle a disease at its source, repairing faulty DNA and allowing the body to fix itself.

Every day 228 Americans die from Alzheimer’s disease, and there is currently no known treatment or cure. Gene therapy offers the ability to permanently correct a disease at its most basic level, the genome, and could offer cures for many conditions that are currently considered incurable. According to Dr. Bill Andrews, the scientist leading the study, “Human telomerase reverse transcriptase (hTERT) is an enzyme whose expression plays a role in cellular aging and is normally repressed in cells, resulting in progressive shortening of telomeres. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer.”

By inducing telomerase, Dr. Andrews and Libella Gene Therapeutics hope to lengthen telomeres in the body’s cells. The clinical trial will treat a limited number of patients using the gene therapy treatment, which has been demonstrated as safe, with minimal adverse reactions in over 186 clinical trials.

Dr. Andrews has been featured in Popular Science, on the “Today” show and in numerous documentaries on the topic of life extension. As one of the principal discoverers of both the RNA and protein components of human telomerase, Dr. Andrews was awarded second place as “National Inventor of the Year” in 1997. He earned a Ph.D. in molecular and population genetics at the University of Georgia in 1981. He has served in multiple senior science and technology roles at leading bioscience corporations. Dr. Andrews is a named inventor on over 50 U.S.-issued patents on telomerase and is the author of numerous scientific research studies published in peer-reviewed scientific journals.

On why the company decided to conduct its clinical research project outside the United States, Libella Gene Therapeutics president Dr. Jeff Mathis said, “Traditional clinical trials in the U.S. can take years and millions — or even billions — of dollars. The research and techniques that have been proven to work are ready now. We believe we have the scientist, the technology, the physicians, and the lab partners that are necessary to get this trial done faster in Colombia.”

The clinical trial is prepping to begin in the first quarter of 2018 and will be conducted at MediHelp Services Clinic in beautiful and tourist-friendly Cartagena, Colombia. The state-of-the-art facility has hosted international public figures including athletes, celebrities and politicians. Dr. Javier Hernandez, MediHelp’s medical director, will oversee the trial.

Colombia’s clinical research regulation is friendly to gene therapy trials, with one of the fastest approval times in Latin America for this kind of research. The trial’s clinical study design; regulatory, operation and logistical support; project management; statistical analysis; and study monitoring services will be provided by LATAM Market Access Inc., a Florida-based clinical research company.

About Libella Gene Therapeutics LLC 
With a mission to reverse aging and cure all age-related diseasesstarting with Alzheimer’sLibella Gene Therapeutics has exclusively licensed the AAV Reverse (hTERT) transcriptase enzyme technology from Sierra Sciences and Dr. Bill Andrews. More information at www.libellagenetherapeutics.com.

About LATAM Market Access Inc.
Dedicated to helping innovative life science companies gather cost-effective clinical data at leading research institutions, the company provides clinical study design; regulatory, operational and logistics support; project management; statistical analysis; and study monitoring services. More information at www.latammarketaccess.com.