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BGRF and SILS Scientists Analyze Viability of shRNA Therapy for Huntington’s Disease – Press Release by Biogerontology Research Foundation

BGRF and SILS Scientists Analyze Viability of shRNA Therapy for Huntington’s Disease – Press Release by Biogerontology Research Foundation

Biogerontology Research Foundation


Friday, December 1, 2017, London, UK: Researchers from the Biogerontology Research FoundationDepartment of Molecular Neuroscience at the Swammerdam Institute for Life Sciences at the University of Amsterdam, and the Department of Neurobiology, Care Sciences and Society at the Karolinska Institute announce the publication of a paper in Translational Neurodegeneration, a BioMedCentral journal, titled RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA.

After many years of development, RNAi therapeutics are nearing the clinic. There are several variants on RNAi therapeutics, such as antisense oligonucleotides (ASOs), short-hairpin RNA (shRNA), small interfering RNA (siRNA), et cetera. The researchers’ paper aimed to answer the question of why RNAi therapeutics for nucleotide repeat disorders (specifically Huntington’s, a devastating genetic neurodegenerative disease), have lost favor in recent years. After a phenomenal amount of excitement, these therapies were hindered by problems like molecular stability, dosing, and transcriptional control of the gene therapeutic construct.

“We compared various RNAi-based therapeutic modalities available for the treatment of Huntington’s Disease and offered mechanistic proposals on how to break through current barriers to clinical development. One key problem has proven to be modulating the expression level of shRNA constructs, which would otherwise be the clear frontrunner among ASOs, siRNAs, and other methods due to duration of expression, dramatically reduced off-target effects, and ease of delivery by adeno-associated viruses that are already approved by the EMA and FDA. We also put forward novel methods of modulating construct expression and avoiding off-target effects” said Franco Cortese, co-author of the paper and Deputy Director of the Biogerontology Research Foundation.

The researchers analyzed available data on the levels of off-target effects associated with siRNA vs shRNA, surveyed emerging strategies to reduce off-target effects in shRNA therapies (such as tough decoy RNAs, or TuDs), and proposed novel methods of controlling shRNA expression, in particular through the use of negative feedback-driven oscillating promoters.

Mechanism of TFEB at the PGC1-a promoter. The PGC1a promoter contains a CLEAR-box that is known to be bound by TFEB, a transcription factor induced during autophagy and lysosomal biogenesis. A construct being the PGC1a promoter CLEAR-box would be induced by TFEB under conditions of intracellular proteotoxicity due to HTT aggregation. By this mechanism, on-demand suppression of HTT could be achieved | Credit: Translational Neuroscience

 

“We proposed two novel feedback mechanisms that 1) activate construct expression stoichiometrically with mutant Huntingtin expression, or 2) only during aggregate-induced autophagy and lysosomal biogenesis. That way, the problem of excessive construct expression may be mitigated. These ideas were inspired by feedback systems used in synthetic biology, and in ‘nonsynthetic,’ naturally occurring biological systems” said Sebastian Aguiar, lead author of the paper.

Readers can read the open-access paper here: https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-017-0101-9.

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About the Biogerontology Research Foundation

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

About the Swammerdam Institute for Life Sciences

The Swammerdam Institute for Life Sciences (SILS) is the largest institute of the Faculty of Science at the University of Amsterdam. The institute comprises biological disciplines including molecular and cell biology, microbiology, plant science, physiology and neurobiology, supported by modern enabling technologies for the life sciences. The research groups of SILS also develop methods in genomics (micro-array, next-gen sequencing, proteomics), bioinformatics and advanced light microscopy technologies. Knowledge from adjacent fields of science, in particular biochemistry, biophysics, medicine, bioinformatics, statistics and information technology make SILS a multidisciplinary research institute with a systems biology approach to the life sciences. SILS’ research objective is to understand the functioning of living organisms, from the most basic aspects up to complex physiological function(s). Biological processes are studied at the level of molecules, cells, cellular networks and organisms. SILS research topics have in common that similar cellular processes and interactions are studied, likewise using similar methodologies and technologies. Therefore SILS scientists often study the same concepts in different biological systems. Within the institute, this leads to exchange of information and extension of research over the borders of different disciplines. Part of SILS research activities are directed to application-oriented research in close collaboration with industry.

Why Rejuvenation Biotechnology Could Benefit You – Article by Nicola Bagalà

Why Rejuvenation Biotechnology Could Benefit You – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà discusses the benefits of Rejuvenation Biotechnology (age-reversing technology).  This article was originally published by the Life Extension Advocacy Foundation (LEAF) .

~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, October 25, 2017

The benefits are many; some are obvious, and some are less so. The ones I’ll discuss in this article are the ones I see as obvious, tangible, immediate benefits for the people undergoing rejuvenation.

Health

We’ve kind of made a rather big deal of this one, haven’t we? Rejuvenation, we have said time and again, is pretty much all about health. The causal link between biological aging and pathologies is well established, and even when we account for the few elderly who are exceptionally healthy for their age, we’re left with the obvious fact that the older you are, the sicker you are, and even the aforementioned exceptions aren’t in the best of shape.

To the best of my knowledge, the number of people who actively wish to be sick at some point tends to be fairly small; so, when you think that a truly comprehensive rejuvenation platform would allow people to maintain youthful health irrespective of their age, the health benefits of rejuvenation become crystal clear. To be honest, this benefit alone would be enough for me, and I wouldn’t even need to look into the other ones.

Independence

Frailty, failing senses, weakness, and diseases aren’t good friends of independence, but they are good friends of old age. That’s why nursing homes exist in the first place to take care of elderly people who are no longer independent. Again, even the few exceptional cases who manage on their own until death don’t have it easy. Having people doing things for you can be nice in small doses, but having to have people doing things for you, not so much. Rejuvenation would eliminate the health issues that make the elderly dependent on others, which is a rather evident benefit.

Longevity

As odd as it may sound, longevity is really just a ‘side effect’ of health, because you can’t be healthy and dead. The longer you’re healthy enough to be alive, the longer you’ll live. Since rejuvenation would keep you in a state of youthful health, the obvious consequence is that you’d live longer. How much longer exactly is hard to say, but as long as you’re healthy enough to enjoy life, it’s safe to say that longevity would be a benefit; you’d have more time and energy to dedicate to what you love doing, and you could keep learning and growing as a person for an indefinitely long time.

You would not have to worry about the right age to change your job, get married, or start practicing a new sport, because your health wouldn’t depend on your age, and the time at your disposal would not have a definite upper limit. If the first few decades of your life weren’t as good as they could have been for one reason or another, you would still have time ahead and a chance of a better future, which sounds more appealing than ten years in a hospice with deteriorating health to me. (Let’s face it: If your life isn’t very good to begin with, a disease is hardly going to make it better.)

Additionally, a longer life would allow you to see what the future has in store for humanity. I wouldn’t be too quick to think the future will be all doom and gloom.

Today’s world is more peaceful and prosperous than it was in the past, and while there’s no certainty it will be at least this good in the future, there’s no certainty that it won’t be worth living in either. I would argue it’s best not to cross our bridges before we get there, and we shouldn’t opt out of life before we actually reach a point when we don’t care for it anymore, if ever.

I don’t think I will ever have a reason to give up on life or get bored with it, but I accept that somebody might think otherwise. Even so, I think being able to choose how long you want to live, and always living in the prime of health, is a much better deal than the current situation of having a more-or-less fixed lifespan with poor health near the end.

Choice

Ultimately, all of these perks can be summarised into one: choice. If we had fully working rejuvenation therapies available and were thus able to keep ourselves always perfectly healthy, regardless of our age, we could choose whether we wanted to use these therapies or not. Those who wish a longer, healthier life could avail themselves of the opportunity and escape aging for as long as they wanted; those who prefer to age and bow out the traditional way could just as easily not use the therapies.

Rejuvenation would give us an extra option we currently don’t have; everyone is forced to face the burden of aging and eventually die of it, for the moment. Being able to choose what we wish for ourselves is one of the most fundamental human rights and an obvious, unquestionable benefit.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

U.S. Transhumanist Party Q&A Session – October 21, 2017

U.S. Transhumanist Party Q&A Session – October 21, 2017

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Gennady Stolyarov II
Martin van der Kroon
Sean Singh
B.J. Murphy


In this interactive question-and-answer session, which occurred at 1 p.m. U.S. Pacific Time on Saturday, October 21, 2017, U.S. Transhumanist Party Officers provided an updated view of the Transhumanist Party’s projects, operations, and achievements, in response to audience questions. Because October is Longevity Month, this Q&A session had a life-extension theme but also delved into various other areas, including how to address conspiracy theories and various approaches toward diet, nutrition, and cultural norms regarding food consumption. The Q&A session has been archived on YouTube here.

The following U.S. Transhumanist Party Officers took part in this Q&A session:

– Gennady Stolyarov II, Chairman
– Martin van der Kroon, Director of Recruitment
– Sean Singh, Director of Applied Innovation
– B.J. Murphy, Director of Social Media

The YouTube question/comment chat for this Q&A session has been archived here and is also provided below.

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Will Today’s Disabled Become Tomorrow’s First Post-Human? – Article by B.J. Murphy

Will Today’s Disabled Become Tomorrow’s First Post-Human? – Article by B.J. Murphy

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B.J. Murphy


Needs will almost always come before wants. When it comes to Transhumanism, the ability to differentiate the two tends to blur, because a need could also be a want depending on the various methods of achieving a need. There’s the “getting by” need and then there’s the “thriving” need.

For the disabled, this dichotomy determines how well they’ll get by in life. If someone loses a leg, then simply getting by could be achieved with a cane, a walker, or even a low-tech prosthetic. However, if this person wishes to thrive in life, then a high-tech prosthetic would be much more preferable, though could also be considered a want rather than a need.

For Transhumanism to work, however, I’d argue that the ability to thrive should be considered an absolute necessity. Thus when it comes to the disabled, I believe they deserve the ability to reach post-humanity before anyone else. In all actuality, this is already happening.

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Why I Fear Aging – Article by Hayley Harrison

Why I Fear Aging – Article by Hayley Harrison

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Hayley Harrison


My mother had leukemia. I really loved her, and she really loved me. When I went to the supermarket at night, she asked me to hurry back, and said she was worried about me. She really enjoyed my company and talking to me. She could talk to me about things she couldn’t tell anyone else. It was like we were best friends. Even though my mom was 74 when she died. I was adopted when my mom was 51 and my dad was 57, so they were already older.

I was closer to her than to any member of my family. Since I lost her, I feel like I’ve lost everything. Aging made her really sick. I found out that the AML leukemia that my mom had mostly affects the elderly.

My father has been in hospital nearly two weeks. He had an operation to remove something on his lung. He’s been unwell for a few weeks now. His appetite has gone right down. He kept sleeping in the chair a lot because of the infection. He’s 81. He’s had tests to see if he has cancer, but we don’t know the results yet.

My friend told me that if my father hadn’t have had the biopsy, his chest infection would have turned into pneumonia, and that would have killed him. The antibiotics have not worked yet. So I keep thinking, “What’s going to happen to him?”. I love my father, too.

If anti-aging medicine were available now, the doctors could have treated my mother as well as my father. My mother’s leukemia was caused by aging, as I discovered. I’d love to be able to talk with my mother and father again.

I don’t want to get old, because I don’t want to get decrepit and sick. The thought of me being so shrivelled up like my parents have got terrifies me.

This is why I’m so motivated to cure aging. I’m trying to do everything I can. I keep hearing a lot that science to cure aging is underfunded. I share science articles and promote science. I’m writing this article to get the message out to all the people about getting aging under medical control.

There’s quite a few people trying to solve the aging problem. Aubrey de Grey and SENS are working on rejuvenation biotechnology. They are doing this by solving the seven deadly causes of aging. These include cell loss, junk inside and outside the cell, extracellular crosslinks, death-resistant cells, and cancerous cells.

Imagine a world where nobody gets old anymore, where everyone is young and healthy. Some people would like to do their favorite sports again, and currently they cannot because of aging.

If I lived forever, I would look to have more confidence. I would try to not be scared of people anymore.

If I were to live longer, I’d imagine I could hang out with a few of my friends in America. I enjoy fashion. I have always wanted to look like a model. I would have the time to select the best clothing and look fantastic.

Hayley Harrison is an Allied Member of the United States Transhumanist Party and the Nevada Transhumanist Party. She resides in the United Kingdom.