Michael Fossel Michael is President of Telocyte

October 18, 2016

The Carpets of Alzheimer’s Disease

Why do Alzheimer’s interventions always fail?

Whether you ask investors or pharmaceutical companies, it has become axiomatic that Alzheimer’s “has been a graveyard for many a company”, regardless of what they try. But in a fundamental way, all past and all current companies – whether big pharma or small biotech – try the same approach. The problem is that while they work hard at the details, they never examine their premises. They uniformly fail to appreciate the conceptual complexity involved in the pathology of Alzheimer’s. They clearly see the technical complexity, but ignore the deeper complexity. They see the specific molecule and the specific gene, but they ignore the ongoing processes that drive Alzheimer’s. Focusing on a simplistic interpretation of the pathology, they apply themselves – if with admirable dedication and financing – to the specific details, such a beta amyloid deposition.

But WHY do we have beta amyloid deposits? Why do tau proteins tangle, why do mitochondria get sloppy, and why does inflammation occur in the first place? Focusing on outcomes, rather than basic processes explains why all prior efforts have failed to affect the course of the disease, let alone offer a cure for Alzheimer’s.

Let’s use an analogy: think of a maintenance service. Any big organization, (university, pharmaceutical firm, group law practice, or hospital) has a maintenance budget. Routine maintenance ensures that – in the offices, clinics, or laboratories – carpets are vacuumed, walls are repainted, windows are cleaned, floors are mopped, and all the little details are taken care of on a regular basis. These are the details that make a place appear clean and well-cared for, providing a pleasant and healthy location. In most offices (as in our cells), we are often unaware of the maintenance, but quite aware of the end result: an agreeable location to work or visit. In any good workplace, as in our cells, maintenance is efficient and ongoing.

That’s true in young cells, but what happens in old cells?

Imagine what happens to a building if we cut its maintenance budget by 90%. Carpets begin to show dirt, windows become less clear, walls develop nicks and marks, and floors grow grimy and sticky. This is precisely what happens in old cells: we cut back on the maintenance and the result is that cells becomes less functional, because without continual maintenance, damage gradually accumulates. In the nervous system, beta amyloid, tau proteins, and a host of other things “sit around” without being recycled efficiently and quickly. Maintenance is poor and our cells accumulate damage.

All previous Alzheimer’s research has ignored the cut back in maintenance and focused on only a single facet, such as beta amyloid. You might say that they focused only on the dirty carpet and ignored the walls, the windows, and the floors. Even then, they have focused only on the “dirt”, and ignored the cut back in maintenance. Imagine an organization that has cut its maintenance budget. Realizing that they have a problem, they call in an outside specialist to focus exclusively on the loose dirt in the carpet, while ignoring the carpet stains, ignoring the window, walls, and floors, and then only coming in once. What happens? The carpets look better for a few days, but the office still becomes increasingly grungy and unpleasant. In the same way, if we use monoclonal antibodies (the outside specialist) to focus on beta amyloid plaque, the plaques may improve temporarily, but the Alzheimer’s disease continues and it is definitely unpleasant. Various companies have focused on various parts of the problem – the floors, the walls, the windows, or the carpets – but none of them have fixed the maintenance, so the fundamental problem continues. You can put a lot of effort and money into treating only small parts of Alzheimer’s, or you can understand the complex and dynamic nature of cell maintenance. Ironically, once you understand the complexity, the solution becomes simple.

The best solution is to reset cell maintenance to that of younger cells. Neurons and glial cells can again function normally, maintaining themselves and the cells around them. The outcome should be not another “graveyard for companies”, but life beyond Alzheimer’s .

 

May 12, 2016

Telomeres: Are They Worth Measuring?

It’s funny how often we make assumptions that are not only wrong, but that we are completely unaware of making. Having spent more than twenty years dealing with the clinical implications of cell aging, telomeres come to mind as an immediate example of this mistake.

Hardly a week goes by without another claim that some particular intervention alters telomere lengths in human patients. Without exception, they are measuring telomeres in peripheral white blood cells. It’s easy to get blood samples and measure telomeres in circulating white cells. Unfortunately, not only are these telomeres the ones that matter least, but (if you’re trying to prove the value of your intervention) they’re almost worthless.

Measuring telomeres in your blood to see how old you are is a bit like looking at your hat size to figure out how tall you are. Whether it’s your peripheral blood telomeres or your hat size, it’s still the wrong measurement for the job.

There are two problems with measuring telomeres in blood cells (even totally ignoring arguments about technical methods, unreliable laboratories, and the mean length versus the shortest lengths of those telomeres).

The first problem is that the blood cells aren’t the key cells when it comes to aging and age-related diseases. If you really want to know where you stand clinically, you should be measuring the telomeres in the endothelial cells lining your coronary arteries, the glial cells in your brain, the chondrocytes in your joints, or several other places more closely related to the most common (and fatal) aging diseases. Few of us are willing to have biopsies taken from our coronary arteries, our brain, or our joints, but just because we are a lot more relaxed about giving a blood sample doesn’t mean that the blood sample is worth getting. It barely reflects what’s going on in your white cells, let alone what is going to end up causing disease and death.

The second problem is a more subtle, but more important. It boils down to this: most of your white cells aren’t circulating in your blood and the ones that do circulate are changing and dividing all the time, making them a poor reflection of what’s happening to the stem cells in your marrow. I wrote an academic review article about this in 2012 and discussed it in The Telomerase Revolution, but let’s look at it here. Imagine you can instantly and accurately measure every telomere in the body, including those in the bone marrow and peripheral venous circulation. Oddly enough, you’d discover that the blood tests aren’t reliable indicators of what’s happening in the marrow.

Let’s say that you measure all of the telomeres at time A and again at time B. In between A and B, you use an intervention such as gene therapy, TA65, mediation, dietary change, or whatever you think might be effective. At time A, you find that the telomeres in the hematopoietic cells of the marrow are 12 kbp long. At the same time (due to stress, infection, poor diet, inflammation, and generally poor health habits) there is rapid peripheral turnover, cell division, and telomere loss in the peripheral blood. As a result, the mean telomere length in the blood sample is only 8 kbp.

We then intervene.

At time B, you find that the telomeres in the hematopoietic stem cells in the marrow are now only 11 kbp long (showing that the patient has gotten older). Also at time B, since we might now have lowered stress, removed infections, decreased inflammation, and generally made the patient “healthier” with whatever intervention we may have chosen, their peripheral cells are now turning over more slowly, dividing less frequently, and losing less telomere lengths once they leave the marrow and enter peripheral circulation, so that the mean telomere length in the peripheral blood sample is now 9 kbp.

We could claim (as many articles do) that our clinical intervention “lengthened the peripheral telomeres!” The truth is that our intervention didn’t lengthen anything and we’re deluding ourselves (and whoever believes our claims). The peripheral telomeres that we sample at time B might be longer than the ones we sampled at time A, but the telomeres of the cells back in the marrow now have shorter telomeres. Our intervention may well have made the patient healthier and we might actually have slowed down the rate of telomere loss, but we definitely didn’t lengthen any telomeres, no matter how proudly we pat ourselves on the back.

Peripheral leukocytes are routinely used to assess telomere lengths (which is fine as far as it goes) and then used to assess clinical interventions, which is overreaching. If we do serial measures of peripheral telomeres every few months for a few years, then the validity will increase somewhat, but peripheral telomere measurements (no matter how often you measure them) are intrinsically an unreliable and invalid biomarker for what we really want to assess, which is “whole body telomere changes” or at least “marrow telomere changes” (in the case of blood cells).

Most of the available literature which suggests that we can slow or reverse telomere losses is – if it’s based on peripheral blood samples – misleading at best and unethical at worst.

April 26, 2016

The Tempo of Alzheimer’s

Hardly a day goes by, and never an entire week, without my seeing yet another article, often a cover article, that suggests we will soon cure Alzheimer’s disease. If articles were anything to go by, then the increasing tempo of those articles, to say nothing of the increases in both research and funding, would suggest we will soon solve the problem. But, publicity, laboratories, and money are not the same as actual clinical results. In fact, the issue is never the amount of resources, but where you aim those resources. If we wish to cure Alzheimer’s, then we need to put some honest intellectual effort into understanding Alzheimer’s. Until then, publicity, laboratories, and funding are only a reflection of wishful thinking. No one ever cured a disease by injecting money into the patient, let alone making them swallow a laboratory, or listen to publicity.

Yet oddly enough, publicity is often perceived as a goal in itself. I see biotech companies who strive to get themselves mentioned on the news, as though that would create success. But whether are on the cover of Time magazine or mentioned in this week’s edition of The Scientist, news stories are never equivalent to a cure for Alzheimer’s or anything else. In fact, I suspect there is often an inverse correlation: the more your drug or your biotech company is mentioned in the media, the less likely it is to get through FDA trials, let alone improve patient care. Just a suspicion, but founded on frequent observations over the past two decades or more.

Some of us want to find a cure, and never mind the kudos.

Other people just want the kudos.

The fact that we hear about another potential “drug that may cure Alzheimer’s disease” on an approximately weekly basis, underscores not only the frantic need for a cure, but the fact that none of the alleged cures actually work. As we say in medicine, when you have dozens of professed cures for a disease, you can be pretty sure that none of them actually do a damn thing. The more strident the claims for “the cure” the more you should suspect an absence of data. When there is a cure and when it works, it will be a single intervention and you’ll know it works because, guess what, it will actually work.

I regret that the media gets caught up in the inflated claims, but it speaks to the public’s hunger to believe. One of these days, it won’t be a claim and it won’t be inflated, it will simply be the facts. When we finally have the facts, it will be because we have shown we can cure Alzheimer’s disease and it will be Telocyte on the cover, but only after we cure Alzheimer’s.

 

February 16, 2016

Unexamined Assumptions

The problem with curing Alzheimer’s is, as with so much of our understanding of aging and age-related diseases, that we make unexamined assumptions. Let me admit that many of our unexamined assumptions are either useful or reasonable. I assume that the sun will come up again tomorrow morning and that’s a useful and reasonable assumption. Useful, in that it allows me to plan my future, reasonable in that the sun has been coming up every morning for quite a while and is therefore likely to do so tomorrow as well. Certain unexamined assumptions are equally justifiable in dealing with Alzheimer’s disease. In the strictly poetic sense, Alzheimer’s certainly is the disease that “steals our souls”, yet no physician or researcher would actually make the assumption that the mind is some vague ethereal quantity that can be stolen by demons, let alone go on to promulgate a theory of Alzheimer’s pathology based on this assumption.

Yet we make exactly that same error, using an unexamined assumption, when we blithely assume that aging is simply the accumulation of damage and, pari passu, that Alzheimer’s disease is simply the accumulation of damaged molecules, be they amyloid, tau tangles, or altered mitochondrial enzymes. This unexamined assumption lies behind almost innumerable multi-million dollar FDA trials, academic papers, and clinical interventions. We assume, without even realizing we have made the assumption, that Alzheimer’s is merely the accumulation of damaged molecules.

We make the same unexamined assumption in looking at other age-related diseases and in the broader field of aging itself. We delve into the details of advanced glycation end-products (AGE), lipofuscin, cross-linking, and other molecular pools showing “accumulative damage”, all the time never realizing that we are making the same fallacy. We are working with completely unexamined (and erroneous) assumptions about how aging works. We naively assume that aging occurs – and age-related diseases follow – merely because things “rust” over time. We age because “molecules fall apart.”

 

Yet the data and logic both say differently. Let me give you a useful analogy: the cell phone. Consider a large pool (several thousand) of people who own cell phones. We know that if we examine any SINGLE cell phone, the best predictor of failure is how long it has been since production. If, however, we want to predict the percentage of failures in any large pool of owners, the best predictor is not time-since-production, but length-of-contract, that is, how often does it get turned over and replaced? Imagine two large pools of cell phone owners. In group A, the cell phones are replaced annually, with a failure rate (at equilibrium) of approximately 1%. In group B, the cell phones are replaced every ten years, with a failure rate (at equilibrium) of approximately 80%. In both groups, the rate of failure of any individual phone is the same. Furthermore, the rate of failure is only marginally related to the “genes”, i.e., whether the phone is an Apple iPhone, an Android, or some other type (a different “allele”). As the turnover rate (contract length to replacement) lengthens, the percent of failed cell phones climbs dramatically, regardless of the failure rate of any individual cell phone. In a pool of cell phones, “aging” is not a matter of passively accumulated damage, but of how actively we replace them.

The same is occurring in molecular pools in biological systems. The key predictor of “denatured” or dysfunctional molecules (e.g., AGE, beta amyloid microaggregates, cross-linking, elastin failure, collagen stiffening, etc) is not the rate of damage but the rate of turnover. In the case of cell aging, when we reset gene expression (reset telomere length) we reset the turnover rates (anabolism and catabolism rates) of all molecular pools to those typical of “young” cells. The outcome is that molecule pool turnover is more than sufficient to deal with typical rates of damage.

Without realizing it, most of us make the mistake of thinking of molecular pools as static and damage as purely accumulative. The reality is that such pools are dynamic and the key dependent variable (as with cell phones) is not the passive rate of damage, but the active rate of turnover.

Unless we understand – and examine – our assumptions, we can never expect to cure age-related diseases. Once we start down the wrong path, all the logic and data in the world can’t make up for the fact that we are looking in the wrong place. It’s time we stopped blaming “demons” and starting thinking carefully.

January 20, 2016

Long Past Time

History provides perspective, probably because we keep repeating it.

Several hundred years ago, smallpox was the scourge of Europe. Treatment, such as it was, consisted of compassion, fluids, and a gamut of various herbs, bark, roots, and fungal preparations, none of which changed the mortality. The diligent healer of the late middle ages tried hard to find just the right plant preparation that would prevent or cure smallpox. By the late 1700’s there had been multiple cases of successful use of cowpox to vaccinate (from the Latin vacca for cow) people, with good results, culminating in Edward Jenner’s publication in 1798. Mind you, like many human discoveries, the process had actually been around a long time, if not particularly well known, well understood, or even believed.

Regardless of its provenance, regardless of its success, the major problem facing those who used vaccination to prevent smallpox was not technology, but common preconceptions. The idea of using an active biological agent – the cowpox virus – flew in the face of the common certainties about how to treat disease. Everyone “knew” that treatment lay in finding just the right plant, whether a root or a bark. Herbalists knew that if they worked hard and put enough resources into finding that perfect mixture of plant compounds, they could cure smallpox. The fact that they were looking in the wrong place, didn’t seem to occur to them.

Back to the future and listen to the echo of history.

We now know that we can reset gene expression in the microglia that play the key role in driving the pathology of Alzheimer’s disease. The data has been accumulating for 20 years, as have the numerous articles in the medical literature and the books and textbooks on this field. And yet, regardless of its provenance, regardless of its success, the major problem facing those who work to prevent and cure Alzheimer’s disease is not technology, but common preconceptions. The idea of using an active biological agent – like the human telomerase gene – flies in the fact of common certainties about how to cure Alzheimer’s. Everyone “knows” that treatment lies in finding just the right drug, whether monoclonal antibody or small molecule. Pharmacology companies know that if they work hard enough and put enough resources into finding that perfect set of molecules, they could cure Alzheimer’s. And once again, the fact that they are looking in the wrong place, doesn’t seem to occur to them.

The echo is hauntingly familiar. Once again, the advance of medicine lay (and will lay) not in finding the right herb (or the right antibody), but in finding a sophisticated and accurate understanding of the disease we are trying to treat. Just as nothing worked in the 18th century until we understood vaccination as a way of preventing smallpox and other viral diseases, so nothing will work in the 21st century until we understand resetting gene expression as a way of preventing and curing Alzheimer’s disease.

It’s time to start looking in the right place.

And it’s long past time to cure Alzheimer’s disease.

December 7, 2015

21st Century Science: Isn’t It About Time?

The other day I was asked about the role of denaturation of a particular protein in aging. It was a typical question that pretty much sums up the problem we have had in understanding (and doing anything about) aging during the past century. The problem is the question hides a flawed premise. It presupposes that molecules simply sit around and accrue damage. Put another way, the problem is that we look at molecules as part of as static pool rather than looking at the dynamic turnover that is the hallmark of metabolism.

Imagine a 1930 Duesenberg that has been lovingly cared for and is in pristine condition, even though it rolled off the assembly line 85 years ago. Compare this to my two-year-old car that already has a few rust spots. Was the Duesenberg better made than my car, that is, did it come with “better genes”? Was the Duesenberg exposed to less damage than my car, that is, did it have “fewer free radicals, less denaturing of its proteins, or a smaller rate of cross-linking”? No. The difference between that “ageless” Duesenberg and my own “aging” car is not the quality of the production line nor the exposure to sun, snow, salt, and dirt. The difference lies exclusively in the dynamics of its care. That Duesenberg was polished, aligned, oiled, repainted, repaired, and “recycled” on a regular basis. My own car is “aging faster” because I don’t care for it as frequently or as carefully as did the owners of that Duesenberg, and therein lies the entire difference between young organisms and old ones.

In aging organisms, it’s neither the genes nor the damage, but the slowing rate of recycling and repair that results in old cells, old tissues, old organisms, and age-related diseases.

Bizarrely and ironically, most people still look at biological systems and ignore the fact that they are alive, that they are dynamic, that they are constantly in flux. We look at a particular molecule – whether beta amyloid, collagen, GDF-11, or a thousand others – and we ignore the fact that these molecules are constantly being created, broken down, and replaced, but instead, we blindly focus on the damage itself. It’s true that as an organism ages any given pool of molecules shows an increase in damage – such as the aggregates of beta amyloid in early plaque formation – but the key is not the damage, the key is the slowing of the metabolic turnover. An accumulation of damage is not static and passively accumulative; it occurs because the rate of turnover falls as a result of changes in the pattern of gene expression. Whether we look at tau proteins, elastin, or any other molecular pool you want to look at, the key to the problem lies not in any particular gene nor in any particular source of damage. The key lies in the rate at which both anabolism and catabolism are replacing those molecules.

We don’t age because we accumulate damage, we accumulate damage because aging permits damage to accumulate.

A doctrinaire attention to “aging genes” and a catalog of one’s favorite sources of molecular damage will never result in cures to age-related disease. The key to intervention lies in the rate of molecular turnover, which responds to changing patterns of gene expression. Those who focus on genes and damage, to the exclusion of molecular turnover and gene expression, are perhaps some of our most highly-educated and intelligent minds of the 20th century…

…but it’s now the 21st century.

It’s time we caught up.

November 10, 2015

Singularity: Why We Age

I hope that all of you will take a look at the free chapter of my new book, The Telomerase Revolution, that has just been posted on Singularity: https://www.singularityweblog.com/why-we-age/#comments. If you find the chapter provocative, please buy the book and read it carefully.

The question of “Why we age” (the title of the chapter excerpted here) is not only a good question, but probably all-but-impossible to answer with any certainty. For one thing, it’s notoriously difficult to do really good, meaningful experiments in answering evolutionary questions. We are stuck using either descriptive cases or experimental models that have short lifespans and arguable relevance to the questions we are asking. Moreover, part of the problem in understanding why we age is that — until recently — we really had no idea what we meant by “age”. There has long been an (often unstated and unexamined) assumption that organisms simply age because of entropy and that specific genes (as opposed to patterns of gene expression) determined aging. Not knowing how aging actually happened naturally led to faulty conclusions about why it happened.

Is my suggestion about “why we age” the correct one? I doubt it, but I suspect that my answer is likely to provide a slightly more realistic start on a reasonable answer because it begins with a more accurate understanding of what we mean by “age”.  If we want to explain why infectious diseases evolve over time, then it helps if we know about bacteria, viruses, chlamydial organisms, fungi, and prions. Once we understand what causes infectious disease, we can talk about the evolution of microbial organisms; once we understand what causes aging, we can talk about the evolution of aging.

 

October 17, 2015

BioViva and Telocyte

The other day, a friend of mine, Liz Parrish, the CEO and founder of BioViva, made quite a splash when she injected herself with a viral vector containing genes for both telomerase and FST. Those in favor of what Liz did applaud her for her courage and her ability to move quickly and effectively in a landscape where red tape and regulatory concerns have – in the minds of some – impeded innovation and medical care. Those opposed to what Liz did have criticized her for moving too rapidly without sufficient concern for safety, ethics, or (from some critics) scientific rationale.

Many people have asked me to comment, both as an individual and as the founder of Telocyte. This occurs for two reasons. For one thing, I was the first person to ever advocate the use of telomerase as a clinical intervention, in discussions, in published journal articles, and in published books. My original JAMA articles (1997 and 1998), my first book on the topic (1996), and my textbook (2004) all clearly explained both the rational of and the implications for using telomerase as a therapeutic intervention to treat age-related disease. For another thing, Liz knew that our biotech firm, Telocyte, intends to do almost the same thing, but with a few crucial differences: we will only be using telomerase (hTERT) and we intend to pursue human trials that have FDA clearance, have full IRB agreement, and meet GMP (“Good Medical Production”) standards.

We cannot help but applaud Liz’s courage in using herself as a subject, a procedure with a long (and occasionally checkered) history in medical science. Using herself as the subject undercuts much of the ethical criticism that would be more pointed if she used other patients. Like many others, we also fully understand the urgent need for more effective therapeutic interventions: patients are not only suffering, but dying as we try to move ahead. In the case of Alzheimer’s disease, for example (our primary therapeutic target at Telocyte), there are NO currently effective therapies, a history of universal failure in human trials for experimental therapies, and an enormous population of patients who are currently losing their souls and their lives to this disease. A slow, measured approach to finding a cure is scarcely welcome in such a context.

And yet…

We have elected to follow the standard approach – with FDA-sanctioned human trials – for three reasons that we see as crucial: 1) we want to ensure safety, 2) we want to ensure efficacy, and 3) we want to ensure credibility. The issue of safety is not a simple one: Alzheimer’s disease is uniformly fatal, so safety might seem to take a distant back seat to efficacy. True, but we see no reason to try an experimental therapy on despairing patients if we inflict easily avoidable risks (by using safe manufacturing processes for the viral vectors). The issue of efficacy is also not simple: you might think that any therapy, even if remotely effective, might be worth trying. True, but we see no reason to use a minimally effective therapy if we can provide a maximally effective therapy with only a bit more forethought and care. The issue of credibility is also not simple: you might argue that if we can cure even one case of Alzheimer’s disease, that will in itself be sufficient. True, but not if no one will believe the clinical results. It may have cured one person, but what about the millions of patients that won’t be treated if no one believes the result?

At Telocyte, we intend to meet all three of those obligations. The therapy must be sufficiently safe to justify the risk in using it in patients who are already desperately ill, it must be sufficiently efficacious to offer more than simple solace or wishful-thinking, and our human trials must be sufficiently credible that our results can be translated into a therapy that can become the accepted standard of care for millions of patients, not simply for a few people.

We applaud Liz’s hopes, her courage, and her enthusiasm as she makes a splash in the news, but Telocyte will take the more difficult path. We don’t intend to create a splash, but a world without Alzheimer’s. It is easy to act, it can even be easy to act with genuine compassion, but it is hard to act effectively and harder still to ensure that compassion is not only the intent, but the final reality.

 

September 8, 2015

The Telomerase Revolution – a Countdown

On Tuesday October 6th, four weeks from today, The Telomerase Revolution will be released by its publisher, BenBella Books. The Telomerase Revolution is a lucid and complete account of what’s been going on in the field, from its beginning to the current revolution in our ability to treat age-related diseases directly and effectively.

Full Cover for blog

As many of you know, the book is a best-seller already, solely on the basis of the number of pre-orders, which is delightful if slightly astonishing. It’s been getting rave reviews both on the grapevine and more officially (on its cover and on Amazon) from scientists and physicians, including from Len Hayflick who called it “superb” when he first read it. The book is dedicated:

To those with minds open to logic and eyes open to data:

May others be as open to you as you are

to the world around you.

 

To those who, aging and suffering,

hear others tell you nothing can be done:

They’re wrong.

 

Intended for the educated public and not merely for the medical or scientific community, The Telomerase Revolution is broken down into eight chapters. The 1st chapter – Theories of Aging – describes “the hoaxes, the myths, and the scientific theories that don’t quite account for everything.” In the 2nd chapter — The Telomere Theory of Aging – I give “an introduction to the theory of aging this book proposes and its historical development, including a discussion of misconceptions about the theory”. The 3rd chapter – Why We Age – is “a short scientific detour into the evolutionary reasons why we age rather than live indefinitely like the hydra”.

In the 4th chapter – The Search for Immortality – I finally turn our attention away from theory and toward the practical aspects matter most, “applying telomere theory to clinical problems”. We learn about what has been going on in the world of biotechnology until now, as we tried to take telomerase to the clinic, as well as why some of these attempts floundered and why other attempts are finally succeeding.

The next two chapters give us a clear explanation of how all age-related diseases cause problems. The 5th chapter – Direct Aging: Avalanche Effects – explains osteoarthritis, osteoporosis, skin aging and other diseases, explaining “how aging cells cause disease in similar cells and tissues around them”. The 6th chapter – Indirect Aging: Innocent Bystanders – gives us a similar clear explanation of the more frightening (and fatal) diseases, such as Alzheimer’s disease and vascular aging (including strokes and heart attacks) by explaining “how aging cells cause disease in different kinds of cells and tissues”.

All of which is fine, but can we do anything about those diseases? The 7th chapter – Slowing Aging – is a practical discussion of “what people can do now to optimize health and lifespan”, as opposed to waiting for the upcoming revolutionary interventions. Those newer interventions are discussed in the 8th and final chapter – Reversing Aging – in which we realize that our ability to cure age-related diseases at the most fundamental level is not waiting in some distant dream, but rather is almost upon us now: “It’s coming soon, and it will change human lives, and society in astounding ways”.

We are about to change medicine forever, by curing diseases that we have long feared, granting compassion and new hope to those who now suffer. This book is but the introduction to the work, as many of us, particularly at Telocyte, take understanding and hard work, and use our knowledge and effort to create cures.

Join us.

September 2, 2015

How much will it cost to cure Alzheimer’s?

Filed under: Alzheimer's disease,Telomerase — Tags: , , — admin @ 10:08 am

Most of us are more concerned with whether we can cure Alzheimer’s at all, than we are with the cost of curing it. You can imagine someone saying that dementia is so horrible that “it doesn’t matter what it costs” to treat or cure it.

Except that it really does matter. Whether it were a treatment or a cure, if it cost a billion dollars a person, it would matter a great deal. Not only couldn’t we – collectively – afford such an intervention, but no single person – as an individual – could afford it either. Well, alright, there are a few people with those resources, but let’s please be realistic. The bottom line is that expense does matter, to you, to me, to us as a society, whether we pay for treatments via our insurance premiums (health plans) or via our taxes (national healthcare systems). Regardless of how we pay, we’d like to find an effective intervention that we can live with, medically and financially.

At the moment, we have the worst of both worlds: we have a medically ineffective set of “interventions” and a financially disastrous burden that we can’t sustain as the costs grow. Our current “interventions” consist of expensive long-term nursing care and a small group of drugs that have no effect on the course of the disease. We spend a lot of money taking care of people who are sliding toward disability and death, and a fair amount of additional money on what are, effectively, placebo medications. Globally and annually, Alzheimer’s Net estimates that we spend a total of about 600 billion dollars (about 1% of the world’s gross domestic product) on treating Alzheimer’s patients, and that cost is steadily growing (and outpacing both inflation and productivity).

Journals, organizations, and blogs harp on predictions of disaster: we can’t afford to keep spending more and more money on Alzheimer’s care as the world population ages. But what is the alternative and how much would such a therapy cost?

If telomerase therapy could cure and prevent Alzheimer’s disease, the costs fall dramatically while the benefits increase even more dramatically. The benefits are clear, but let’s consider the costs. The first cost we can cut is that of nursing care: if I can care for myself, I don’t need any nursing care, let alone expensive, long-term, full-time care in a nursing home or “assisted care living center”. This removes most of our costs, particularly the costs currently borne by national health care systems (taxes), as well as by private insurance (premiums). The remaining cost – that of medication for treating Alzheimer’s disease – is currently about $10 billion dollars as a global market. While these drugs are not – in comparison with other drugs – all that expensive, part of their cost depends on market size. Not all AD patients are on these drugs, largely because both patients and physicians recognize that their ratio of benefit to risk is small, so why bother spending money on drugs that have risks and no real benefit? On the other hand, if we have a therapy that cures Alzheimer’s and has few risks, then patients would be eager to take such a therapy, which is why telomerase therapy will – on a per patient basis – be quite reasonably priced.

Compare two drugs: one for progeria and one for Alzheimer’s dementia. At any given moment, we estimate that there are about 50 progeric children and about 50 MILLION (or more) Alzheimer’s patients in the world. Now, imagine that we develop a drug whose research and human trials cost 50 million dollars. In order to pay off these costs of development, that would mean that if it only worked for progeria, it would cost a million dollars per progeria patient, but if it were used for all Alzheimer’s patients, it would cost only a dollar per Alzheimer’s patient. In general, the larger the patient population, the cheaper the drug costs per patient. Fifty million patients makes it easy to amortize the costs of development: we spread the costs out and dilute them. Therapy become cheap.

The reality, however, is that there are other costs. Among them are the cost of producing the drug (once you pay for its development) and the costs of administering the drug. In a rough way, production costs also go down as the patient population goes up. There are economies of scale in producing 50 million doses compared to producing only 50 doses. The cost per dose goes way down. On the other hand, telomerase therapy will require a high degree of quality control, so while there will be enormous economies of scale, production will still be expensive in order to be safe and effective. Administration costs (distribution, hospital overhead, professional services, etc.) are less amenable to economies of scale and will be almost “fixed”. In many cases, the costs of administering a drug far outweighs the costs of producing a drug, and this is likely to be true of telomerase therapy.

Even acknowledging the many unpredictable factors, we can come up with an estimate for the cost, within an order-of-magnitude (order-of-magnitude in the scientific sense: not below one tenth and not more than ten times). The cost of producing a single dose of telomerase therapy (ignoring profit, retail distribution, and administration costs) would probably not be much more than it is for other currently available (and ineffective) drugs, having a probable production cost of perhaps $100 per patient. It will likely take 1-3 doses to treat a patient initially, who will then need retreatment every 5-10 years.

If it cures Alzheimer’s, then it’s a good price to pay.

 

 

 

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