Gary Hudson on removing senescent cells and treating cancer

Original author: Steve Hill
  • Transfer


Oisin Biotechnologies is a biotechnology rejuvenation company that a few years ago received seed funding from the Methuselah Foundation and the SENS Research Foundation .

The company is currently working in the field of selective destruction of senescent cells using drugs called senolithics . Senescent cells are one of the causes of aging , and as they accumulate in the body, they contribute to the development of age-related diseases. Their periodic removal from the body has long been proposed by the SENS Research Foundation, and it is Oisin that is working on new technologies in this area.

The technology that Oisin uses is different from other approaches, such as small molecule preparations used in Unity Biotechnology , in one key aspect. The method they use is very flexible and can be programmed to destroy any type of cell based on the protein they express. Standard markers for the isolation of senescent cells are p16 , for cancer cells p53 .

Today we present you an interview with Gary Hudson, CEO of Oisin Biotechnologies, who 15 years ago was one of the first to support the creation of the Methuselah Foundation, and who is now working to market one of the first rejuvenation technologies based on the SENS program. Oisin is moving forward rapidly and is currently conducting a round A of attracting venture capital to bring technology into clinical trials.

Interview


Hill : For those who are not familiar with your technology, could you give a brief description of it?

Hudson : We use a simple way to induce cellular apoptosis. We can destroy cells using apoptosis, and this method is quite effective. The choice of the type of cells to be destroyed depends on the specific age-related disease. At present, we target cells expressing p16 and p53 proteins.

The technology uses two components. First, we create a DNA construct containing the promoter that we want to target. This promoter contains an inducible cell self-destruction gene, iCasp9 . Then we encapsulate this DNA in a special liposome.known as LNP - Fusogenic Lipid Nanoparticle. LNP protects plasmid DNA during transport through the circulatory system and quickly infuses into the cell membrane.

Such a liposomal vector is non-selective, it has no preference for senescent cells, it will penetrate almost all cell types. After entering the cell, the plasmid DNA is in the cytoplasm. It remains in a dormant state if there are no transcription factors in the cell that will be associated with the promoter. If this happens, iCasp9 is synthesized.

iCasp9 is activated only in the presence of a small molecule- dimeraiser, this dimeraiser causes the halves of the iCasp9 protein to join together, which immediately causes apoptosis. This process ensures the destruction of targeted cells, but not all other cell types. So far, we have not recorded any effect on other cells.

We also improved both the promoter and effector, which would give the base technology even more interesting and useful properties, but for reasons of intellectual property protection we can only talk about them at the end of the year.

Hill: The Senolithic attracted considerable attention last year, since Baker and the others showed for the first time that the approach worked fundamentally. Many research groups work in the field of small molecule preparations to remove senescent cells. What are the advantages of your system compared to a more traditional approach based on small molecules?

Hudson : We believe that different populations of senescent cells may require different approaches for the desired level of body cleansing, sufficient to produce noticeable results. Each of the various projects using completely different approaches may find a market niche.

Personally, I like our approach with particular selectivity in the absence of noticeable side effects in relation to other cells. This is exactly the problem that supporters of the use of small molecules constantly have to pay attention to.

Hill : ß-galactosidase and p16 are often used as targets for senolithic, but there is a fear that these substances are secreted not only by senescent cells. For example, stem cells express p16, but they are not senescent. Have you done research on the effect of senolithic on stem cell populations, and how would you solve the issue of potential side effects?

Hudson: We have not conducted such studies. We are currently relying, so to speak, on our eyes. Baker and others, from Kirkland to Kaiser, showed an improvement in health and average life expectancy as a result of the use of various senoliths. If the stem cell population had suffered greatly from various drugs of this kind (from transgenically induced apoptosis to dasatinib and quercetin , and FOXO4-DRI peptides ), we would have expected the negative effects of treatment, but so far this has not happened.

Hill : Cytomegalovirus over time more and more exacerbates the load on the immune system, which sends him a growing number of memory T-cellsbut can not get rid of it. Assumptions were made about the effectiveness of periodic cleansing of the body from these ineffective T-cells. Have you considered using your technology for such purposes?

Hudson : Yes. We began work in this direction, and the project is particularly liked by the Aubrey de Gray from the SENS Research Foundation, but we currently have no planned experiments. This project is on our list, along with several other immunological experiments.

Hill : Likewise, can your system be used against infectious diseases like HIV to destroy infected cells?

Hudson : Maybe. Similar solutions were proposed by Tod Rider from the DRACO project , which was presented atSENS6 in 2013.

Hill : A number of experiments suggest that removing senescent cells increases healthy life expectancy, but the question remains open with respect to overall life expectancy. Have you begun a study on longevity in mice, and which mice do you use?

Hudson : We would like to conduct a similar study, but it has not yet begun. First, life expectancy studies are relatively expensive, for obvious reasons. Secondly, we hope to attract an assistant from the side of researchers to participate in the management of the experiment, but have not yet found it. Finally, our main goal is to bring the drug to clinical trials and phases 1 and 2with human trials. All other parallel projects lead to a later implementation of this goal.

I'm not sure which line of mice or rodents might be best suited for the study of life expectancy, but I know that our goal will be experiments on old animals (for mice this is more than 70-80 weeks old at the time of treatment). It is not easy to find a sufficient number of such animals, and we may have to grow them ourselves, which will further delay the project.

Hill : What progress has been made in targeting p53 instead of p16 in the fight against cancer?

Hudson: Results above all expectations. We were able to remove 90% of the tumor mass in just 24-48 hours and reduce metastases in models of both human prostate cancer 10 times and mouse melanomas 20 times in the same time. Many commentators have expressed concerns about the use of p53 due to the fact that it is expressed in many cells, but in real experiments this theoretical fear was not confirmed

Hill : We observed how many anti-cancer drugs were used in the removal of senescent cells. Many focus on BCL proteins that help cells resist apoptosis; Have you considered using BCL as a target for your drug?

Hudson: Not. But the advantage of our approach is the simplicity of testing various types of targets for a promoter. As soon as we have the necessary resources, we will expand the list of goals.

Hill : We have seen an increased interest in increasing the number of macrophages H1 and H2 in the treatment of diseases such as heart disease, Parkinson's disease, damage to the peripheral nerve. H1 macrophages usually cause inflammation and recruit other immune cells to the area of ​​damage or infection, while H2 macrophages regulate the process and promote healing. However, as a result of aging, the balance is disturbed, and H1 macrophages cause too much inflammation. Can your approach be used to selectively destroy H1 macrophages and create a more conducive environment for recovery?

Hudson: If there is a promoter, we are more likely to be able to do this. I am not an immunologist, so a specialist with the necessary qualifications will have to identify the target for the promoter, after which we could try, again, if there are resources for the experiment.

Hill : In conclusion, would you like to say something to our readers? How can an ordinary person help progress in rejuvenation technologies?

Hudson : As I noted earlier in an interview with Fight Aging !: The

public interest in anti-aging therapies should, sooner or later, lead to a policy change. Informing lawmakers about the public importance of work to restore and regenerate the body is the first step towards recognizing the FDA as an aging diseaseagainst which treatments can be developed.

In conclusion, I want to point out that SENS technologies are too important to depend only on a small number of our supporters who have dedicated their lives, financial resources and reputation. We need more researchers, companies and funding. Join and do it!

Translation done Pattern, SENS Volunteers group

Also popular now: