Rejuvenation: immediate prospects
Startups relevant to the rejuvenation biotechnology industry in 2018
Fight Aging!: Request for Startups in the Rejuvenation Biotechnology Space, 2018 Edition
Translated by Evgenia Ryabtseva
For links, see the original article
Over the past couple of years, there has been a noticeable shift in priorities in the field of rejuvenation research. Much more attention is being paid to this industry and the most promising areas have made – or will make in the near future – a qualitative transition from non-profit laboratory or philanthropic financing to commercial start-up companies and venture financing.
A growing community of philanthropic investors and a fairly large number of venture funds are currently interested in supporting startup companies whose founders are implementing rejuvenation approaches based on the SENS (Strategies for Engineered Negligible Senescence - strategies for artificially minimizing physiological aging) model of fundamental damage restoration.
The abbreviated list includes: Kizoo Technology Ventures, Methuselah Fund, the Longevity Fund, Mann Bioinvest and Apollo Ventures. Others will join them over the next couple of years, as interest in this area is growing rapidly.
It should be noted that there are more than enough sources of financing waiting in the wings and ready to finance any trustworthy company dealing with rejuvenation issues during the first years of its existence.
In fact, at the current stage, such funding is much easier to obtain than philanthropic funding of the early stages of laboratory research. Specialists who own technologies capable of making the transition described above can only act decisively and do it. Do not wait, you need to contact the venture community and assess your chances of success. Many different interesting approaches to the treatment of aging as a medical condition are already very close to being suitable for commercial development. Below are the most promising developments, scientists working on which should not delay with requests for funding.
More effective approaches to evaluating the results of senolytic therapy
The emergence of methods of senolytic therapy aimed at destroying cells that have entered the phase of physiological aging will be a great achievement in the field of medicine. However, how can we determine if they work and, if so, how well?
It is possible to assess the severity of a standard set of manifestations of the disease, but this is a second-rate approach to determining the actual number of cells that have entered the phase of physiological aging, and, accordingly, the severity of their effect on the body.
To date, all effective methods for estimating the number of such cells involve obtaining a tissue sample, and since tissue injury contributes to the physiological aging of cells, there is doubt about the expediency of biopsy-based approaches. We need better approaches that will allow us to develop non-invasive or minimally invasive tests to quantify the physiological aging of cells.
In just a couple of years, dozens of companies will appear promoting various methods of senolytic therapy, but at the same time, it seems that no one is thinking about the need to develop viable commercial tests for physiological aging. In this extremely important niche, there is a single startup company and one or two research groups with interesting ideas. This state of affairs needs to be changed.
Rejuvenation and medical tourism
If any representatives of the first generation of potential senolytic drugs demonstrate their effectiveness in clinical trials, this will open up huge commercial opportunities in the field of medical tourism. The same thing may happen in the next few years, when new approaches to gene therapy based on CRISPR technologies will provide the possibility of reliable transfection of large fractions of target cells.
There are four or five target genes, such as myostatin and follistatin, which can form the basis of very interesting approaches to activating therapy. The number of healthy people who are potentially interested in undergoing anti-aging or activating therapy far exceeds the number of patients who need treatment for certain medical conditions.
Quite a large number of research groups that are part of the scientific community working in the field of longevity, including BioViva, Ascendance Biomedical and Libertas Biomedical, are slowly moving forward in solving various issues related to the launch of medical tourism. At the same time, they all consider this task more difficult than it might seem at first glance. The main task is to find a mechanism that will make foreign clinical research and treatment transparent, cost-effective, safe and attractive, creating a fast-growing market that functions in synergy with the introduction of anti-aging therapeutic interventions and body activation technologies into clinical practice.
Rejuvenation of the immune system
The immune system is involved in so many processes and aspects of aging that the restoration of its age-related functional disorders would have a huge impact on health in the later stages of life. There are potentially viable approaches to influencing each of the many components of this puzzle, and most of them are still very far from commercial development. These approaches include:
– selective destruction of damaged immune cells or even the entire immune system, if it can be carried out without an effective, but very toxic modern approach consisting in the use of high doses of immunosuppressants;
– periodic administration of large doses of patient-specific immune cells;
– impact on the reduced activity of populations of bone marrow stem cells responsible for the formation of immune cells;
– restoration of the activity of the thymus, where the maturation of T-cells occurs, to stimulate the formation of new T-lymphocytes.
Disorders of the immune system are a significant component of age-related decrepitude, and all of the above approaches are worthy of advancement in the direction of clinical practice.
Destruction of glucosepane crosslinking and supporting technologies
In the near future, Spiegel Lab employees will identify enzymes that break down crosslinking of glucosepane, after which, without any doubt, they will create a startup company. It is quite possible that there are many more approaches leading to a similar result, such as the use of small molecules.
The destruction of crosslinking will reverse the processes of reducing the elasticity of blood vessels and skin aging. The emergence of such techniques will create a huge market with great opportunities for competition. Screening of drugs does not require excessive financial costs, but getting started with glucosepan remains a matter of narrow specialization.
This direction provides real opportunities for any group that is able to adapt to the developing infrastructure of research dedicated to working with glucosepane and make some progress. It should also be noted that in this direction there is still the same problem with evaluating the results of potential senolytic action: while companies will begin to develop new therapeutic approaches, how can we assess how much a person is affected by cross-linking glucosepane without isolating its fragments for analysis?
Non-invasive or minimally invasive assessment methods are extremely important and will be in great demand when the first therapeutic approaches appear.
More effective, faster and cheaper getting rid of beta-amyloid
Modern immunotherapeutic approaches to the elimination of beta-amyloid in Alzheimer's disease are characterized by huge costs both for development and implementation. They can become a platform for future methods of eliminating other twenty or so types of amyloid accumulating in aging tissues, but only with a simultaneous radical reduction in financial costs and an equally pronounced acceleration of progress towards some really working method. We need something better.
Researchers need to broaden their horizons and develop fundamentally new approaches, such as the drainage of cerebrospinal fluid proposed by Leucadia Therapeutics or the catalytic bodies (catabodies) of Covalent Bioscience. If successful, both of these approaches can be much more economically viable. Currently, specialists should look for such innovative approaches.
Getting rid of lysosomal debris
A number of companies, including human.bio and Ichor Therapeutics are working on the introduction of several first biotechnological approaches to the destruction of specific problematic forms of metabolic waste (cell waste) that complicate the functioning of lysosomal mechanisms for processing cellular debris or otherwise disrupt the functioning of cells.
This is a small step towards a big goal: there are a huge number of problematic compounds and, accordingly, a huge number of options for eliminating these components of the pathogenesis of age-related diseases. Ichor Therapeutics adheres to the model of choosing a single compound strongly associated with a particular disease. At the present stage, this strategy can be used by about a dozen companies working on different targets.
Targeted blockade of telomere elongation
The victory over all types of cancer with the help of a single therapeutic approach based on the blockade of telomere elongation is a very plausible solution to the problem of too many forms of the disease, a lack of researchers and the currently prevailing trend of using highly specific therapeutic approaches.
If we want to see significant progress in getting rid of cancer in the foreseeable future, first of all it is necessary to change the existing model of research and development. The scientific path to universal antitumor therapy has already been clearly outlined: it is necessary to selectively block the effects of (a) telomerase and (b) mechanisms of alternative telomere elongation, combining this with mechanisms of targeted delivery of therapeutic agents.
At the present stage, it is very unlikely that any company will be able to directly develop a fully unified approach, however, even solving part of a common problem or identifying the final component of the system would be of great value in itself. Work on this area should begin with one of the well-known methods of telomerase activity disruption, but we will see how events will develop.
Introduction of cell therapy methods in the field of rejuvenation
To date, the absolute majority of cell therapy methods used in practice do not provide rejuvenation of patients. They make it possible to achieve temporary improvements, mainly due to the suppression of inflammation, accompanied by a secondary moderate increase in regeneration activity and improvement of tissue vital activity.
Transplanted cells die quickly and the results obtained are due to the functioning of signaling pathways during the period of cell preservation. More advanced methods of cell therapy of the expected new generation will allow replacing lost or affected cell populations for a long period of time. At the same time, the transplanted cells will survive and integrate into the tissues, ensuring the restoration of the functions of certain organs and biological systems.
Moreover, there are a number of other, less obvious possibilities that may be useful. These include induction of cell pluripotency in vivo, the above-mentioned introduction of immune cells compatible with the patient's body, as well as strategies for intensive cell replacement. In general, regenerative medicine based on the use of cells is an industry that has hit the "ceiling" and must go beyond it to move to a qualitatively new level.
Reliable, high-coverage gene therapy platforms
A big obstacle to the introduction of the most promising methods of gene therapy into clinical practice through medical tourism is the reliability of the degree of cell coverage of methods for delivering therapeutic agents into the adult body.
The existing methods are not reliable enough and do not ensure the delivery of therapeutic agents into the fraction of cells, especially stem cells, large enough to form truly irreversible changes in the recipient's body. Success in this direction will be a revolution in medicine and in the field of human wellness technologies.
Apparently, the scientific community is on the verge of solving this problem in several ways at once. If any of these methods are introduced into clinical practice, it will be enough to launch an explosive growth in the scale and capabilities of the market for gene therapy methods.
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