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Alzheimer’s Disease Reversed by Editing a Single Gene – Article by Steve Hill

Alzheimer’s Disease Reversed by Editing a Single Gene – 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 our allies at the Life Extension Advocacy Foundation (LEAF) on April 13, 2018. In this article, Mr. Hill reviews a new study published in Nature that supports the idea that Alzheimer’s disease research efforts should target the ApoE4 gene, and not consider the ApoE3 gene as much, even though  previous research that focused on the ApoE3 gene cured Alzheimer’s disease in mice models. This is a promising step forward for Alzheimer’s research.

~Bobby Ridge, Assistant Editor, July 2, 2019

Researchers at Gladstone Institutes in San Francisco report that a gene variant associated with Alzheimer’s works differently in mice and humans, and they also demonstrate how modifying this gene could potentially prevent the plaques associated with Alzheimer’s from forming and damaging the brain. The new study was published in the journal Nature in January 2018 [1].

An ApoE3 gene variant is associated with Alzheimer’s disease

The gene apolipoprotein E3 (ApoE3) has a variant known as ApoE4, which is associated with the development and progress of Alzheimer’s disease. People with just one copy of the ApoE4 gene are at twice the risk as people without this gene variant. Some people even have two copies of the ApoE4 gene, which makes their risk of Alzheimer’s a staggering twelve times greater.

Both the ApoE genes produce their own forms of ApoE protein, which differ in structure. The ApoE4 protein is fragile and fragments because it cannot function in the same way as the regular ApoE3 protein in human nerve cells. These fragmented protein pieces are associated with the increased production of amyloid-β peptides and tau phosphorylation that are typical of Alzheimer’s disease.

The researchers wanted to find out how ApoE4 is linked to Alzheimer’s disease. They considered the possibility that the increased amyloid-β and tau phosphorylation from the fragmentation of ApoE4 drives disease progression. Another possibility involved the negative consequences of a lack of ApoE3 proteins, as they were replaced by the ApoE4 variant. The team also considered a combination of both of these possibilities.

The team investigated these potential answers by examining the effects of ApoE3 and ApoE4 on human nerve cells. Neurons were created by using pluripotent stem cells taken from volunteers who had either two copies of ApoE3 or two copies of the ApoE4 gene, and the researchers programmed these cells to become the desired type of neuronal cell.

The team compared the ApoE3 and ApoE4 neurons against neurons that were unable to produce either type of the ApoE protein. They discovered that neurons that produced no ApoE protein worked the same as those that produced ApoE3. This confirmed that it was not a lack of ApoE3 causing the problem but that ApoE4 protein alone was linked to Alzheimer’s disease.

This finding also sheds light on why treatments for Alzheimer’s that work in mice fail to translate to humans. The production of amyloid-β in mice is not influenced by ApoE4; this means that treatments that prove effective in mice may not work in humans, as the mouse models of the disease do not emulate the ApoE4-related form of Alzheimer’s that humans get. However, therapies that focus on reducing amyloid-β have worked in mice [2], so while ApoE4 functions differently in mice and humans, this is not the full story of Alzheimer’s. This research does, however, clearly show a way in which mouse models differ from humans, helping to guide future research.

Converting ApoE4 to ApoE3

The results of the study suggest that therapies that seek to modify the ApoE4 gene protein before it fragments might be a way to combat Alzheimer’s. This is how traditional medicine would generally approach the problem, treating the symptoms and not the cause.

However, the researchers took this one step further to a far more robust solution. Rather than simply attempting to treat the consequences of having an ApoE4 gene producing sub-par proteins, they completely removed the problem by using gene therapy to edit the genes and convert them from ApoE4 to ApoE3.

The converted genes ceased to produce the unstable ApoE4 protein and produced the stable ApoE3 version of it instead. This served to correct the problem at the root rather than trying to slap a band-aid on the consequences.

Conclusion

With so many failures to combat Alzheimer’s disease, it is easy to become disillusioned. We have seen mice cured of the disease numerous times, but these cures have failed to translate to humans. These new findings help to progress knowledge in the field and offer potential new ways to defeat Alzheimer’s.

What is refreshing about this study is how the researchers have opted to attack the problem at the root cause: the production of misfolded proteins that lead to the progression of the disease. It is becoming ever more clear that if we are going to make progress on ending age-related diseases, we must target the aging processes themselves, which cause these diseases.

Literature

[1] Yuang, Y. et al. (2018) Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nature Medicine doi:10.1038/s41591-018-0004-z

[2] Hu, X., Das, B., Hou, H., He, W., & Yan, R. (2018). BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions. Journal of Experimental Medicine, jem-20171831.

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, 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.

What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

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Scott Emptage


I will be 85 sometime in the early 2070s. It seems like a mirage, an impossible thing, but the future eventually arrives regardless of whatever you or I might think about it. We all have a vision of what it is to be 85 today, informed by our interactions with elder family members, if nothing else. People at that age are greatly impacted by aging. They falter, their minds are often slowed. They are physically weak, in need of aid. Perhaps that is why we find it hard to put ourselves into that position; it isn’t a pleasant topic to think about. Four decades out into the future may as well be a science-fiction novel, a faraway land, a tale told to children, for all the influence it has on our present considerations. There is no weight to it.

When I am 85, there will have been next to no senescent cells in my body for going on thirty years. I bear only a small fraction of the inflammatory burden of older people of past generations. I paid for the products of companies descended from Oisin Biotechnologies and Unity Biotechnology, every few years wiping away the accumulation of senescent cells, each new approach more effective than the last. Eventually, I took one of the permanent gene therapy options, made possible by biochemical discrimination between short-term beneficial senescence and long-term harmful senescence, and then there was little need for ongoing treatments. Artificial DNA machinery floats in every cell, a backup for the normal mechanisms of apoptosis, triggered by lingering senescence.

When I am 85, the senolytic DNA machinery will be far from the only addition to my cells. I underwent a half dozen gene therapies over the years. I picked the most useful of the many more that were available, starting once the price fell into the affordable-but-painful range, after the initial frenzy of high-cost treatments subsided into business as usual. My cholesterol transport system is enhanced to attack atherosclerotic lesions, my muscle maintenance and neurogenesis operate at levels far above what was once a normal range for my age, and my mitochondria are both enhanced in operation and well-protected against damage by additional copies of mitochondrial genes backed up elsewhere in the cell. Some of these additions were rendered moot by later advances in medicine, but they get the job done.

When I am 85, my thymus will be as active as that of a 10-year-old child. Gene and cell therapies were applied over the past few decades, and as a result my immune system is well-gardened, in good shape. A combination of replacement hematopoietic stem cells, applied once a decade, the enhanced thymus, and periodic targeted destruction of problem immune cells keeps at bay most of the age-related decline in immune function, most of the growth in inflammation. The downside is that age-related autoimmunity has now become a whole lot more complex when it does occur, but even that can be dealt with by destroying and recreating the immune system. By the 2030s this was a day-long procedure with little accompanying risk, and the price fell thereafter.

When I am 85, atherosclerosis will be curable, preventable, and reversible, and that will have been the case for a few decades. There are five or six different viable approaches in the marketplace, all of which basically work. I used several of their predecessors back in the day, as well. Most people in the wealthier parts of the world have arteries nearly free from the buildup of fat and calcification. Cardiovascular disease with age now has a very different character, focused more failure of tissue maintenance and muscle strength and the remaining small portions of hypertension that are still problematic for some individuals. But that too can be effectively postponed through a variety of regenerative therapies.

When I am 85, there will be an insignificant level of cross-linking in most of my tissues, as was the case since my early 60s. My skin has the old-young look of someone who went a fair way down the path before being rescued. Not that I care much about that – I’m much more interested in the state of my blood vessels, the degree to which they are stiff and dysfunctional. That is why removal of cross-links is valuable. That is the reason to keep on taking the yearly treatments of cross-link breakers, or undergo one of the permanent gene therapies to have your cells produce protective enzymes as needed.

When I am 85, I will have a three-decade patchwork history of treatments to partially clear this form of amyloid or that component of lipofuscin. I will not suffer Alzheimer’s disease. I will not suffer any of the common forms of amyloidosis. They are controlled. There is such a breadth of molecular waste, however: while the important ones are addressed, plenty more remain. This is one of the continuing serious impacts to the health of older individuals, and a highly active area of research and development.

When I am 85, I will be the experienced veteran of several potentially serious incidences of cancer, all of which were identified early and eradicated by a targeted therapy that produced minimal side-effects. The therapies evolve rapidly over the years: a bewildering range of hyper-efficient immunotherapies, as well as treatments that sabotage telomere lengthening or other commonalities shared by all cancer cells. They were outpatient procedures, simple and quick, with a few follow-up visits, so routine that they obscured the point that I would be dead several times over without them. The individual rejuvenation technologies I availed myself of over the years were narrowly focused, not perfect, and not available as early as I would have liked. Cancer is an inevitable side-effect of decades of a mix of greater tissue maintenance and unrepaired damage.

Do we know today what the state of health of a well-kept 85-year-old will be in the 2050s? No. It is next to impossible to say how the differences noted above will perform in the real world. They are all on the near horizon, however. The major causes of age-related death today will be largely controlled and cured in the 2050s, at least for those in wealthier regions. If you are in your 40s today, and fortunate enough to live in one of those wealthier region, then it is a given that you will not die from Alzheimer’s disease. You will not suffer from other common age-related amyloidosis conditions. Atherosclerosis will be reliably controlled before it might kill you. Inflammatory conditions of aging will be a shadow of what they once were, because of senolytic therapies presently under development. Your immune system will be restored and bolstered. The stem cells in at least your bone marrow and muscles will be periodically augmented. The cross-links that cause stiffening of tissues will be removed. Scores of other issues in aging process, both large and small, will have useful solutions available in the broader medical marketplace. We will all live longer and in better health as a result, but no-one will be able to say for just how long until this all is tried.

Scott Emptage is an anti-aging activist in the United Kingdom. 

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.