Part II : A Survey of For-profit Research Centers
How much money is going into aging research? The information is not so easy to come by. This interview estimated that companies working on medical solutions to aging have a market cap of $300 billion as of 2018. I’m guessing this number is rather too optimistic. This Business Insider article counted $850 million in venture capital funding in 2018. That’s million with an m–a lowball estimate, it seems. It’s safe to say the answer lies somewhere in the vast ocean between these distant shores.
I have not found comprehensive data on startups in anti-aging medicine, so this survey is incomplete and biased according to my own familiarity with the companies and their programs. And the more important disclaimer: I have strong ideas about what the end of aging will look like, and this has colored the view I present of each company below. If you know of companies that you think should be on this list, please make suggestions in the Comments below.
Geron is ancient by present standards, founded in Silicon Valley in 1990 by Michael West, who was already an advocate of telomerase therapies. They are long established, with market cap of $260 million but only 15 full-time employees. Clearly, their mission is research rather than production. Over the years, they have turned their telomerase expertise into drugs that block telomerase, useful as a cancer treatment, since most tumors cannot continue to grow without telomerase.GRN163L (Imetelstat), is a drug under development that targets telomerase. They apparently made the decision years ago, when they sold the IP for their best telomerase promoter to Noel Patton that telomerase was too dangerous to let out of the cage. I wonder if even now they realize that was a mistake.
Elysium Health is Len Guarente’s company selling a formula of NR and pterostilbene. Pterostilbene is a “better resveratrol”. Interest in both resveratrol and the NADH pathway grew out of Guarente’s long-time study of sirtuins. I believe that modest health benefits have been established from this approach, but NADH is so well studied that if there were dramatic results, we would have seen them by now. And NR treatment is not without risks.
Sierra Sciences (Bill Andrews) is focused on small molecules that promote expression of telomerase, lengthening telomeres and preventing cell senescence. Screening hundreds of thousands of chemicals in vitro for telomerase activity, they came up with TAM 818, which is now for sale in New Zealand as a skin cream. In an unrelated approach, they are offering a clinical trial (in a South Pacific island where regulatory agencies permit) using gene therapy to add copies of telomerase. My personal opinion: Several years ago, I believed that telomere shortening was an aging clock of primary importance, but then a large Danish study demonstrated that the scatter in telomere length is greater than the consistent drift toward shorter telomeres with age. I still think elongation of the shortest telomeres is an anti-aging strategy, but no longer regard it as centrally important.
Telocyte (Michael Fossel) is experimenting with telomere elongation to prevent Alzheimer’s disease and even to restore neurological function. Fossel understood aging and had the vision to appreciate the role of telomere erosion more than 20 years ago, and I have the highest respect for him, but from what I know, AD as a target seems to be mismatched to the biology of telomeres. Telocyte has recently announced a strategic partnership with Maria Blasco, a Spanish researcher whose lab has produced most of the biggest milestones in telomerase therapy.
Rejuvenate Bio The Harvard laboratory of George Church was early in recognizing the potential for CRISPR technology to bring gene therapy into mainstream medicine. Rejuvenate Bio is offering a gene therapy program to dogs who are at genetic risk for mitral valve disease, a congenital heart disorder. It’s cheaper than human trials, with less liability when something goes wrong, and it’s a viable lab for gaining experience and honing technique. [Writeup at FightAging!]
Stem cell therapy
Stem cells are among the most promising technologies we have for regenerative medicine. I’m surprised not to find more companies doing basic research, but there are lots of companies bringing the present (hit-and-miss) state of the art to patients. Advanced Cell Technologies, a leader in the field, is now a part of Astella Therapeutics. Apceth Biopharma delivers stem cell technologies in the health marketplace but doesn’t seem to do much research. Pluristem Therapeutics and Brainstorm Cell claim to have active research programs. I have found no companies focused on the potential of stem cell therapies for extending lifespan.
Clinics and personalized medicine
AHNP (Apollo) acquired MPI, which was Dale Bredesen’s vehicle for bringing his Alzheimer’s protocol to the medical public. I give AHNP special mention because I believe that Bredesen’s program is not only the first credible treatment for bringing brains back from AD; further, I think that Bredesen’s Alzheimer’s preventative program doubles as a comprehensive program to slow aging. With individualized programs based on a battery of diagnostic tools, it’s a new model for how to do preventive medicine. I believe the program has transformative potential, but translation to the clinic has led to growing pains at AHNP. They can’t train new staff fast enough, and they’ve fallen behind explosive demand from new patients. Their software interface is buggy and there’s a backlog of requests for personal support, but they’re aware of the problems and building capacity as fast as they can.
Leucadia Theraputics has a diagnostic and treatment model for Alzheimer’s Disease based on drainage of amyloids from the brain, and physical blockage of the drainage pathway.
L-Nutra is Valter Longo’s company, offering programmed, packaged meals that provide some of the benefits of fasting with less of the hunger and deprivation.
Human Longevity is mining hospital records and genomic data to look for correlations. They offer testing and counseling to customers, then base their study on their customer base.
ASDERA is Knut Wittkowski’s small but important New York think tank. Like other math geek operationss, they are using computers to mine data for patterns that lead to new drugs. But unlike the others, they are not relying on the black box approach of neural networks. Wittkowski is an old-school statistician, familiar with an arsenal of classical statistical tests, choosing with judgment and expertise applied to the caseat hand. Both approaches are computationally intensive. The difference is whether computations are guided by expertise and experience or by an algorithm that directs its own search toward a human-defined goal. Think of it as Artificial Intelligence vs Human intelligence, if you like. Supervised learning vs a purely algorithmic search. Time will tell which approach yields more leads to actual treatments. I’m rooting as usual for the underdog, the classical against the avant garde. Neural networks may yield a prescription, but you don’t know if it’s a fragile artifact of the particular data you used or a robust new truth about biochemistry, and the computer can’t tell you what it’s thinking. With more human participation in the process comes more understanding of where the result comes from and (at least) a guess as to what it probably means.
Acturx is another data mining project, headed by Edouard Debonneuil. Debonneuil’s background is in actuarial science for insurance companies, and he is mining insurance records of millions of patients. By correlating prescription records with health outcomes, they look for unknown benefits from known drugs.
Everon Biosciences was founded in 2010 by Andre Gudkov, with awareness of programmed aging built into their strategy. Gudkov believes that endogenous DNA damage in somatic cells is a primary clock driving diverse aging phenotypes. A prominent kind of DNA damage is the duplication of regions of DNA that contain no genes (retrotransposons, including LINEs and SINEs). NRT1 is a drug in development that inhibits the enzyme that makes the copies. Another locus of research is senescent cells as emitters of signals that drive inflammaging. But while other companies are racing to find agents that selectively kill senescent cells (leaving normal cells undamaged), Everon has focused on the innate immune system, including neutrophils and macrophages. Their hypothesis is that the innate immune system takes care of senescent cells when we are young, but the system has a fixed lifetime capacity, and once its limit is reached, senescent cells accumulate and the vicious cycle of increased inflammation begins. EBS3899 is a molecule they are testing for its ability to sensitize macrophages to senescent cells, and it seems to work better in vitro than in vivo.
Unity Biotechnology works on one molecule at a time, exploring their potential to relieve arthritis or degeneration of the eye or age-related disease in lungs, liver, kidneys and the CNS. UBX0101 is their arthritis drug, in trials. Other drugs at earlier stages of development target senescent cells and cognitive decline.
Oisin Biotechnologies is searching senolytic drugs, joining a crowded race to minimize toxicity to normal cells while efficiently eliminating senescent cells.
Biomarkers and Age Clocks
Spring Discovery and InSilico Medicine. In order to study anti-aging interventions, we need to evaluate them, and the traditional measure — waiting for experimental subjects to die — is too slow. This is the reason the Horvath clocks are so important. His algorithms based solely on methylation profiles are the best measures of human biological age we have so far. Spring and InSilico are both trying to improve on that, combining other measures along with methylation, and using neural network analysis — the black box of AI — to look for patterns that evade human brains. These two companies are unrelated and working on opposite coasts, but if there’s a difference between their goals or methods, I have yet to understand what it might be. [ScienceBlog article on InSilico]
Signal Molecules in Blood Plasma
[Background in my blog from 2 years ago.]
Jesse Karmazin’s Ambrosia was an ambitious start-up, turned to object lesson in hazards of the fast track. The basic premise is sound — that blood factors from the young are able to set back the clock of the older animal (or person) in whom they are introduced. But which blood factors? And how much is needed? And how many treatments would be needed before the body would set its own clock back, and start producing the youthful factors by itself? Karmazin’s plan was to ask these questions with clinical trials funded by his subjects, people willing to pay thousands of dollars for two transfused pints of blood from a young person. This past winter, the FDA stopped him in his tracks.
Tony Wyss-Coray’s Alkahest has taken the same promising premise and followed with more care toward a promising future. In the early 2000s, Wyss-Coray was one of the Stanford pioneers of parabiosis. Originally, Alkahest seemed to be headed in the same direction as Ambrosia, offering small quantities of young blood to wealthy clients afflicted with Alzheimer’s. But now they’ve made some important discoveries about the active ingredients that give young blood its rejuvenating power. They are well aware that it’s all about dosage–that some plasma components need to be downregulated and some upregulated to turn old blood to young (and perhaps turn old bodies to young…). They’ve coined the term “chronokines”, key proteins that increase or decrease with age, and they’ve identified a few of these and launched clinical trials for macular degeneration and, Parkinson’s, and dementia. I’m impressed. My only suggestion is that they should be alert to the possibility that the interaction among these chronokines might be non-linear and, perhaps, surprisingly complex.
Google CALICO is well funded, but their relevance to progress in the field is hard to assess. We might guess that their research direction follows the intersts of Cynthia Kenyon and David Botstein, i.e., understanding the genetic contributors to aging in worms and yeast cells. They are partnering with Harvard’s Broad Institute and California’s Buck Institute in basic research. They are in it for the long haul, building biochemical knowledge from the ground up. If someone doesn’t get there first, we may be very glad for their industry in another 10 years.
Google has also invested in shorter-term drug development through Verily Life Sciences, with partnerships that include GlaxoSmithKline. Personal note: I see a danger here, in which the company that we trust to direct us to the best information sources is allied with an industry that has done so much to promote its products with disinformation about health.
Lyceum is Michael Rose’s effort to commercialize research he’s done on the genetics of aging in fruitflies. The web site claims a systems approach, which sounds right to me, but no details are offered at this early stage.
resTORbio is developing variants of rapamycin, which is perhaps the most credible anti-aging drug commercially available. Rapamycin is not patentable, the main reason we see more research on variants and less on rapamycin itself.
CHAI = California Healthy Aging Initiative
Game-changer on the horizon
Activists in California are gathering support for a ballot initiative to provide $12B in state funding for anti-aging research over the next 12 years. CA is one of the states in which the people can create legislation directly with their votes; and in 2004, this process was used to appropriate $4B for stem cell research. Promoters of CHAI are trying to build on this precedent. But they face a dilemma. Gathering signatures and educating the public is an expensive proposition. They will need a broad coalition of research interests in the field to get their measure off the ground. But of course, these organizations will want to write the text in such a way as to direct future funding to themselves. The grass-roots activists who are energizing this initiative believe that adding incrementally to institutions that are already well-funded is less likely to generate disruptive technologies than many small grants to individuals and start-ups with idiosyncratic theories of aging. I like the idea of supporting small people with big ideas, perhaps because I are one. This is a science still in its exploratory phase, where we do not have a definite idea what will work, and there are competing theoretical frameworks to guide us. Once the proof-of-concept is complete, it’s appropriate to pursue the “D” part of “R&D”, and for that, industrial-scale research is the most efficient course.
My perspective on the state of research
I believe that aging is regulated under epigenetic control, but that the biochemical language of epigenetics is complicated, and it will be a slow road indeed if we persist in studying one intervention at a time. The time is right for open science, open communications, interdiciplinary collaboration, and the testing of treatments in sets of 2 and 3 and 4. (If we study only treatments in isolation, we miss the boat; but if we try to study 5-way and 12-way interactions, the number of combinations will overwhelm our neural networks–both silicon and wetware.)
I continue to promote DataBETA because I think that it is a methodology for exploring the landscape from a perspective of radical empiricism, and point us in new directions. DataBETA is looking for a university partner with experience in large-scale trials and otherwise is funded and ready to launch.
Our knowledge of biochemistry comes mostly from a reductionist framework. We understand cellular systems better than we understand organs and tissues. We understand least of all the global signaling and interactions by which the body coordinates its growth, its homeostasis and (I believe) its aging. The primitive state of systems biology counsels an empirical approach.
I‘m glad to see money and talent pouring into aging research, and it’s refreshing to see how much of it goes to people without theoretical preconceptions. But many of the engineers and computer geeks coming into aging science are experienced in a world where problems can be split into manageable parts—divide and conquer. My guess is that aging will be refractory to this approach, and will yield in the end to a multi-pronged but holistic therapy.
I gave up on the stock market years ago, the pride of the mathematician laid low by the surprises of the real world; but if I were a gambling man, I’d bet on Bredesen/Apollo. There’s a solid core of biochemistry under a mountain of clinical data, and sparked to life with a bit of inspired guesswork. They are modest (or prudent) enough to claim ‘only’ to have cured Alzheimer’s, but I would be eager to see methylation tests that relate their protocol to the best aging clock we’ve got.