Request for Startups in the Rejuvenation Biotechnology Space, 2017 Edition

Some lines of rejuvenation research after the SENS model of damage repair, alongside a number of other useful compensatory technologies such as a select few gene therapies, have reached the point at which clinical development can make the leap to for-profit development in startups. There is a sizable amount of money out there on the sidelines waiting for this; investors of all stripes, from biotech veterans and new longevity-science-focused funds to angel communities. The message in this post is primarily intended for entrepreneurs and those out there in the scientific community with relevant work that is approaching the stage at which translational research and development can begin in earnest. We all know how hard it is to raise money for important, transformative research within the world of grants and philanthropic funding. If you have credible work and can put together a credible team, then look to venture funding sooner rather than later. That is my advice in the present environment.

I am interested in seeing the following types of technology emerge into for-profit development in the next few years, to join those like senescent cell clearance that are already well underway. The list is in no particular order of preference. If any of these cover your area of work and you have the ability to build a way to treat aging and its causes, then I want to hear from you. If you are working on anything else that is in the near future rejuvenation therapy list or the SENS portfolio, and is closer to realization than I expected it to be, then I want to hear from you. There is a growing community of investors out there with a considerable interest in seeing this field of research and development prosper.

Better Senescent Cell Assays

Cellular senescence is a cause of aging. Clearing these cells will turn back or slow the progress of many age-related conditions, and should extend healthy life spans at the same time. The current assays used to evaluate the presence of senescent cells in tissue are, shall we say, good enough for getting the job done in a laboratory setting when the goal is research and development. However, they are too manual, time-consuming, and costly for the near future in which near every adult will want to know the state of their cells before and after a clearance procedure, and in which senescent cell levels in specific tissues will become an important diagnostic tool for a range of age-related conditions. The existing assays are also poorly available to patients, where they exist at all in the current laboratory services market. Better, cheaper, faster assays are needed: ultimately, this should be something that is no more costly or challenging or restricted than is a blood sugar test kit that is sold over the counter.

Restoration of the Aged Thymus

There are numerous studies in mice demonstrating the ability to restore some fraction of lost immune function via transplantation or regeneration of the thymus, such as via foxn1 signaling or using forms of cell therapy and tissue engineering. A straight transplantation of a youthful thymus extends life in aged mice. These approaches work by enabling a higher rate of maturation of new T cells, which lessens some of the constraints that act to cause immunosenescence, the age-related decline in the immune system. This work is too promising not to be ushered rapidly towards the clinic, and some of the relevant lines of research are certainly close enough to make the leap.

Safe Ablation of Immune Cells Free from Side-Effects

Removing all or near-all circulating mature immune cells is an approach that has been used to cure multiple sclerosis, an autoimmune condition in which the immune system becomes misconfigured to attack crucial parts of the patient's cellular biochemistry. The immune system repopulates itself with fresh cells after such a comprehensive removal, but without any of the particular problems that produce autoimmunity. This should work equally well against any autoimmunity that doesn't have a strong genetic cause - or at least it would be very surprising to find an acquired autoimmunity that survived such a treatment. Similarly, many aspects of age-related immune dysfunction either involve autoimmunity or some other form of acquired imbalance and malfunction in immune cell populations. Removing all of the cells should help to turn back the clock to some degree, sweeping away that disarray. Unfortunately even the best of the present methods used to ablate immune cells so completely are essentially forms of chemotherapy: they have significant side-effects, and are probably unacceptably risky for older patients. To move ahead, methods of side-effect-free targeted destruction of all forms of immune cell are required: any such technology would immediately be applicable to autoimmunity and immunosenescence in the old.

Packaged and Reviewed Medical Tourism Services

We are on the verge of the clinical availability of worthwhile therapies that either compensate for or treat the causes of aging. This will happen outside the excessively regulated US medical system, in regions where only safety has to be demonstrated. BioViva and Sierra Sciences would like to offer follistatin gene therapies for example, and the first senolytic drugs to clear senescence cells are well categorized enough to be offered by any clinic just as soon as people put their minds to it. The availability of stem cell therapies developed in much the same way following the turn of the century. Despite that history, the medical tourism market is still very immature at the present time. There is a lack of organizations to provide informed reviews of clinics and procedures and to package the various needed portions of the product into one service: flight, stay, therapy, follow-up, and so on. When the flow of patients is small, as is the case for many medical conditions, it might make less sense to enter this market. The new therapies to treat the causes of aging will be beneficial to half of the population presently alive, including all of those presently in good health, however: an enormous market.

Gene Therapy with Reliable, Well-Established High Levels of Cell Coverage

As the initial BioViva data hints at, and as has been demonstrated in animal studies, the challenge for gene therapy is that without sufficient coverage of cells, and especially stem cell populations, the effects are small or transient. The first broadly useful gene therapies in the matter of aging are likely to be the myostatin and follistatin therapies that increase muscle mass, thereby slowing or somewhat compensating for the progression of sarcopenia. The first attempts in humans, either gene therapy or antibody blockade, are nowhere near as impressive as the results in mutant lineages in which all cells have the altered or missing genes, however. In this dawning CRISPR-powered era of gene therapies, there is first and foremost a great need for reliable, high levels of cell coverage. Any significant step towards solving this problem can be applied to the first classes of enhancement gene therapy, and thereby make them far more useful and valuable.

Small Molecule or Enzymatic Glucosepane Cross-Link Breaking

Cross-links in the extracellular matrix are a significant cause of aging, contributing to, for example, the chain of consequences that passes through arterial stiffening, hypertension, and finally cardiovascular disease and death. Also loss of skin elasticity, which most people seem to care about a lot more, somewhat irrationally. Comparatively little work is taking place to produce therapies that can break the dominant type of cross-link in humans, glucosepane, and most of that work is being funded by the SENS Research Foundation. Now that glucosepane has been efficiently synthesized, the door is open, however. Any group with knowledge of this area of biochemistry can put in practical work towards the production of good tissue models, antibodies suitable for glucosepane cross-link assays, and small molecule or enzymatic cross-link breakers. The SENS Research Foundation teams are not the only research groups out there who have expressed interest in this area in the past, and a little competition would be a welcome sign of progress.

Comments

Layperson guess, but couldn't Oisin's or CellAge's genetic technology selectively activate FOXN1 in a mouse (or dog) thymus?

Posted by: Jim at December 28th, 2016 12:36 AM

Better senescent cell assays, see cellage at lifespan.io as this is their first goal. Develop and provide freely a new assays to detect these cells and thus improve research.

Posted by: Steve h at December 28th, 2016 4:05 AM

@Jim: Since Oisin's DNA is not inserted in the cell nucleus but is floating in the cytosol, it's degraded in a few days or weeks. It suffices for senescent cell killing, but it's too short-term for other uses like the one you suggest.

@Steve: Probably donations to CellAge will experience a boost after SRF campaign ends.

Posted by: Antonio at December 28th, 2016 7:07 AM

@Antonio - in that thymic rejuvenation experiment I think they only temporarily activated FOXN1, so Oisin's tech (I'm guessing plasmids) should perhaps suffice.

Posted by: Jim at December 28th, 2016 8:31 AM

Having read a bit more about promoters over the last few weeks, I imagine that Oisin are just using the presence of the P16 promoter to begin transcription of a suicide gene in their plasmid, much like oncolytic viruses being developed for cancer try to be specific by relying on promoters selectively expressed in the cancer cells.

Posted by: Jim at December 28th, 2016 9:03 AM

@Jim: Ah, ok. Then maybe it can work.

Posted by: Antonio at December 28th, 2016 11:00 AM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.