Interview with Gary Hudson about the new anti-aging biotechnology

For the last couple of years, we have seen rapid progress in various areas in the fight against sensate cells . Recently, UNITY Biotechnology made a loud statement , and the extension of life by removing senescent cells was demonstrated in mice. This is a great time for SENS, Strategies for Engineered Negligible Senescence , because one of the important technologies for rejuvenating the body, which the organization has been promoting and supporting for more than a decade, is now actively moving in the direction of clinical trials. This allows attracting previously inaccessible venture financing and raises public awareness about the possibility of treating aging.



Today's article is devoted to a new company that cleans the body of senescent cells - Oisin Biotechnologies , founded and funded by Harry Hudson and Matthew Scholz. Oisin researchers have perhaps the best available approach to removing senescent cells and, I think, have approached its implementation in humans closer than UNITY. Early prototypes of Oisin's work were known to representatives of the SENS Research Foundation shortly after they began work — in a small community everyone is aware of everything, but initial funding in 2014, first from the Methuselah Foundation , and a few months later from the SENS Research Foundation, was provided by the efforts of the David Gobel of the Methuselah Foundation This funding made it possible to successfully test the principle approach in mice, and a new round of investment was held the year before last to begin a new phase of clinical trials. I am pleased to announce that Fight Aging! He participated in this round, providing little help in an important research project. Let me now turn to Harry Hudson of Oisin Biotechnologies, who will explain what approaches they use to develop rejuvenation technologies.

Interview

Risen : What is Oisin Biotechnologies, under what conditions did you meet and decide to dedicate your next startup to this?



Hudson : Oisin was founded by two people, Matthew Scholz, who proposed the basic scientific approach of our first technology and me, together with the Methuselah Foundation and later the SENS Research Foundation, who provided funding as business angels. I act as CEO while the company is at the initial stage.



Matt and I met a few years ago at a life extension meeting - the Bay Area Health Extension Salon at the evening seminars (organized by Joe Betts-LaCrox from Mousera ). It is noteworthy that my friend Judy Campisi from the Buck Institute was the main speaker that evening. Matthew was the first speaker to introduce his then new company in Immusoft gene therapy. Judy spoke about the interesting work that was published by Mayo Clinic and showed a significant positive effect on the removal of senescent cells in transgenic mice. Coincidentally, the continuation of this study was published in the journal Nature and demonstrated a significant extension of life as a result of the removal of senescent cells in mice with normal aging.



After discussion, Matthew and I speculated on possible ways to destroy senescent cells that could be used on humans. (By this time, Matthew had been researching gene therapy vectors for a long time and had worked with the non-viral cell self-destruction gene developed in Baylor and already used in humans). Matthew said that, in his opinion, we could use a certain liposomal vector , which he discovered earlier, in combination with the apoptosis gene to destroy senescent cells in humans. He said that he was too busy and absorbed in working at Immusoft to start another project, and since this technology was too different from Immusoft technology, working on it would be an undesirable distraction for him. But the more we talked about it, the more we liked this idea. Finally, I just said, “This needs to be done. If you provide a description of the technology, I will finance everything myself. I will be the CEO and raise the missing funding in order to check if the method works. ” So we issued a license for the liposome vector, applied for a patent and created the first prototype.







Kidneys, inguinal fat and lungs



Risen : You cleanse the body of senescent cells; what approach do you use and how far have you come?



Hudson : Our approach is quite different from most attempts to destroy senescent cells. Our potential therapy includes two components. First, it is a nucleotide sequence that includes an activator present in the cells that we want to destroy, and a self-destruct gene that causes apoptosis. This nucleotide sequence can be as simple as that mentioned in Baker's work and destroys cells with the expression of p16 protein , or more complex, for example with the inclusion of logic that ensures the selectivity of its work. The second component is a unique liposomal vector capable of delivering our nucleotide sequence to almost any cell in the body. This vector is unique due to a combination of efficacy and supposedly high safety even in large doses.



There is not an obvious but significant difference between our approach and others. Cell recognition is carried out at the expense of the nucleotide sequence , and not of the vector. Liposomal vector does not have any preference for senescent cells. It delivers the nucleotide sequence in both healthy and senescent cells. Recognition is not at the expense of markers on the surface of cells or other external signs. As Matthew likes to say, “we destroy cells based on what they have in mind, not on the surface.” So, if the activator of our nucleotide sequence (for example, the p16 protein gene) is active in a cell during therapy, the next part of the nucleotide sequence, the self-destruct gene, will be transcribed and cause apoptosis . However, if the p16 gene is not activated in a particular cell, nothing will happen, and soon the nucleotide sequence delivered by us will be split by the body. This provides our therapy with high selectivity and, importantly, the temporary nature of the effect. Since we do not use the virus to deliver the nucleotide sequence, and our liposomal sequence is not immunogenic , we hope that it can be used repeatedly in one patient.



So far, we have demonstrated that our vector and nucleotide sequence can effectively and selectively destroy senescent cells in cell culture, and we can target it to insensitive cells in vivo in mice that received chemotherapy . The next step is to demonstrate that we can recognize senescent cells in the same way as in the Mayo Clinic study, but in the translated model - without using the INK – ATTAC transgenic mice. After all, humans are not transgenic mice. With all the achievements of their work, it is purely academic interest; the medicine applied by them on mice will not help people much. We hope to receive the first data in the course of the next research this year.



Risen : How is your approach different from the UNITY Biotechnology approach?



Hudson : I have no direct data regarding the activities in UNITY; you and I probably read the same articles about their work. They seem to be concentrating on the development of small molecules . As I said earlier, we use the technology of gene therapy for temporary exposure. In other words, we effectively destroy senescent cells using a gene program that we load into our liposomal vector.



The advantage of our approach compared to using small molecules is that, if necessary, we can very quickly reconfigure our treatment method to destroy a specific type of cell in certain circumstances, or adapt it to ignore certain types of cells - and all just by changing the nucleotide sequence that we deliver. We have a platform for selective destruction of cells based on very specific and easily changeable genetic criteria. A medicine based on small molecules does not have this flexibility.



Risen : You just had a round of investment, what are your plans for next year?



Hudson : As I already mentioned, all the elements of our approach work well, so it’s time to put all the pieces together and do the work necessary to turn a promising technology into a medicine that changes people's fates. We hope to conduct several in vivo studies in the near future to assess the effect of therapy on aging due to various reasons. If funds and time allow, we will also try to determine the optimal doses, the number of courses of administration needed to drastically reduce the number of senescent cells in the body, and so on. We would also like to conduct a large-scale study of life expectancy in mice and, possibly, other animals. We will seek cooperation with pharmaceutical companies that focus on specific diseases recognized by the FDA, such as COPD , BPH, and others.



Risen : What do you think about the global SENS program and the goal of victory over aging?



Hudson : This topic interests me since adolescence, when we really flew to the moon (not in the sense of Google projects). When they asked me what I wanted to do in life, I usually and only half jokingly said “fly to the stars and live forever” - borrowing this approach from science fiction writer James Blish . But I found that in 1969 there was no hope for progress in the fight against aging, so I turned my attention to space and became one of the first entrepreneurs in this field. After 45 years in it, I am ready to devote time to finding an engineering solution to the problem of aging.



I was the first major contributor to the SENS project. I participated in the financing of the SENS and Methuselah Mouse Prize conferences. I believe that the main approach of SENS to treating aging as an engineering problem — repairing, replacing, restoring functions — will lead to an increase in the period of healthy life and bring us closer to the “ second space ”.



Risen : How do you think SENS technology should be brought to clinical trials?



Hudson : This is a tough question. Personally, I am not particularly interested in the usual pharmaceutical way to clinical trials. This does not mean that we (or rather, our partners from the pharmaceutical industry) will not go this way, but its cost must be assessed taking into account the need to attract public attention to these technologies as soon as possible. Therefore it is necessary to consider alternative ways. One of the areas that depends little on the traditional path is veterinary medicine and animal treatment. Development of our new strategy is an important part of my short-term plans, another important area is the next stage of attracting investments in financing the initial stage of the company's development, which took place in 2016.



Risen : If everything works fine and all project participants get rich, what's next?



Hudson : In fact, my entire share in Oisin will go to my non-profit organization (which will be announced soon) and will focus on promoting the latest technologies in translational medicine . But, although I hope to make a profit on behalf of our investors, my goal in setting up a company was to promote real anti-aging therapies. If we succeed, we have good chances to earn. But money is important for me only because it will allow us to move faster to the next problem of aging, and this is what we will do.

Conclusion

If Oisin is a successful company, its success will lead to additional funding from the Methuselah Foundation and the SENS Research Foundation, as well as individuals who already provide tremendous support to the science of life extension. People who, like myself, understand that the only rational idea was to spend the surplus funds to finance technologies of radical life extension. What is the meaning of money for the sick and the dead? The real value of money nowadays is the ability to spend it on creating technology to defeat aging and disease. If more people understood this, we would have achieved much more.

Comments by Michael Rae

I am very enthusiastic about the veterinary route of Oisin, than I thought (and think) about testing senoliths per se as part of the Robust Dog Rejuvenation (radical rejuvenation of dogs).



First, and most importantly, the state of science is now much better: we used to have interesting, but still limited results for a single senolithic protocol, and now we have a lot of research with several results (including longevity) using different models of aging and different procedures (INK-ATTAC, 3MMR-p16, dasatinib / quercetin, Navitoclax) conducted in more or less normal mice. Oisin has already done some preliminary work on mice and plans to conduct tests for life expectancy. This is a very strong scientific base, tested on mice, and it will allow to work on other organisms.



Secondly, Oisin technology is much closer to true anti-aging biotechnology for removing senescent cells: it directly targets cells based on their aging markers (rather than interfering with metabolism), and has a cleaner (in principle) implementation mechanism (avoiding interference with metabolic pathways relied on by other cells).



Thus, it is much more realistic to translate it into a real rejuvenating therapy for people or even dogs than dasatinib / quercetin, - a perspective that I look at with great enthusiasm.



In principle, this can be a real rejuvenating biotechnology of a person, especially if it is more specific for senescent cells, or several different targeting options can be developed. The veterinary route is (a) scientifically valuable in and of itself, (b) will cause an intense public response and lead to the acceptance of the reality of intervening in aging, and (c) is a potential strategy that allows for a faster transition to use on a person.



There are still a lot of problems in RDR: RMR (radical rejuvenation of mice) per se is still the main standard, and if we had a complete panel of rejuvenating biotechnologies needed for its implementation, (a) it would be much preferable to use the technology, in principle similar to Oisin than small molecules, and (b) the mouse remains the best organism for the test. It takes two years to take an older mouse and double the remaining lifespan; The equivalent of a dog is about eight years old.



But I completely agree on the main thing - the day when people first see their dogs (and their friends' dogs) living much longer and healthier (and possibly obviously rejuvenated) after receiving anti-aging procedures will be a turning point in the enthusiasm and recognition of aging as treatable. fatal disease. The prospect that worries me a lot and should worry us all.



Translation done Pattern, SENS Volunteers group