About Ira S. Pastor
Ira S. Pastor – Chief Executive Officer; Bioquark Inc. (www.bioquark.com) a unique life sciences company that is working on novel bio-products for human regeneration, disease reversion, and biologic age reversal
Mr. Pastor has over 25 years of experience across multiple sectors of the pharmaceutical industry including pharmaceutical commercialization, biotech drug development, managed care, distribution, OTC, and retail; Previously served as VP, Business Development for phyto-medicine development company Phytomedics Inc., raising $40 million of private equity, consummating over $50 million of licensing deals, and bringing lead auto-immune botanical drug candidate from discovery stage to Phase III development; Prior to that, employed by SmithKline Beecham Pharmaceuticals working in sales, marketing, and business strategy positions. Mr. Pastor has also served as Vice President of Corporate Development for the pharmacy benefit management company Prescription Delivery Systems (acquired by Cigna Health Insurance); MBA, Temple University; BS, Pharmacy, Rutgers University
Mission: To bring an end to many of the most devastating ailments associated with human disease, degeneration, and death.
Ira S. Pastor
CEO
Bioquark Inc.
pastor@bioquark.com
www.bioquark.com
Questions & Answers
Q: Could you explain in plain language what medical products BioQuark is pursuing; i.e. combinatorial biologics and bio-products for human regeneration? How is this approach to regenerative medicine different from stem cell therapy? Can this approach be synergistic to make our own stem cells work better? Or to curtail rogue cancer cells without harsher treatments like chemo and radiation? Will these be off-the-shelf medicines? Will they be less expensive than personalized cell therapy? And the biggest question from a patient perspective - how far away is this therapy(ies) from clinical trials and eventual access? What will be the first product developed and tested by Bioquark, Inc.?
A: Bioquark Inc. (www.bioquark.com) is focused on the development of novel peptide based biologics, with the goal of inducing natural, endogenous regeneration and tissue repair in human beings.
As some background to the Bioquark story:
We currently live on a planet with other organisms, that from a health and wellness perspective, are much further advanced than humans.
Many lower organisms can replace lost or damaged organs and tissues that are identical in structure and function to the original, effortlessly regenerating a wide variety of tissues, including spinal cords, limbs, hearts, eyes, and even parts of their brains. In a similar fashion, many of these same species possess fascinating skills for repairing and reversing cellular and genetic damage. Cancer, as an example, is found to be extremely rare in species displaying an efficient regenerative mechanism, even under the action of potent carcinogens. In many cases, when cancer does occur, tumors have been found to spontaneously remodel and integrate into their surroundings as normal, healthy tissue. Some of these organisms can even age, and then return to a youthful state later on in life. Needless to say, humans are pretty weak when it comes to accomplishing any of these feats.
What we discovered in the early days of Bioquark’s research program, was that these themes (what we call the 3 R’s - Regeneration, Reorganization, and Reanimation) were all intimately connected by an underlying capability in such organisms to 1) turn back biologic time in targeted tissues, and 2) start the development process over again. And while stem cells were a part of the process, there were many other important biologic forces at work simultaneously.
Hence Bioquark Inc. was formed with a goal of creating a single therapeutic platform, based on peptide therapeutics, which could help humans to mimic these abilities for purposes of health and wellness.
While these 3 dynamics are present in many different forms throughout nature and across species, in humans these abilities are found co-existing in the synergistic biochemical dynamics found within activated ooplasms (the cytoplasm of the egg following fertilization); hence Bioquark's program focuses on deriving novel biochemical materials from these ooplasms and applying them in human health.
We refer to these materials as “combinatorial biologics” because they represent NOT single drug entities, but defined, standardized mixtures of biologic materials (peptides, microRNA, etc.) that the egg uses to undertake the range of its very important responsibilities related to taking care of the new embryo which include: resetting cellular age, reprogramming DNA to eliminate genetic and epigenetic damage, remodeling of organelles, protection from inflammatory, oxidative, and infectious damage etc.
While ooplasm based reprogramming has been studied for the past 60 years in the petri dish in the forms of cloning, IVF, and most recently in the production of iPSC cells, Bioquark has decided instead of going in the direction of the stem cell model, to instead develop off-the-shelf biologics for direct therapeutic application in humans.
Hence our core product looks like any typical biologic drug material (insulin, interferon, etc.) , and will be administered via a range of traditional delivery vehicles SC, IM, intra-thecal, etc. depending on the target indication or tissue.
The egg is a very important cell as it is not only the “mother” cell of future stem cells, but it needs to fulfill a variety of support responsibilities until those stem cells are able to operate on their own. Hence we see a lot of synergy not only in direct therapeutic use of such biologics, in reprogramming diseased tissues to a healthier state, but also in the guidance of stem cells in more complex forms of regeneration, including those required in 3D organs and limbs.
While as a U.S. based biologics company we are still considered early stage from a traditional development perspective, we do have technology transfer licensees in other territories ex. U.S. that are more rapidly pursuing human clinical applications of our technologies, in territories with more conducive regulatory environments.
Q: What is your opinion of stem cells for the treatment of rheumatoid arthritis? What type of stem cells might work best and why?
A: I think that there may be some short term benefit in the anti-inflammatory / immuno-modulatory effects of the paracrine / trophic “cocktails”, that the various stem cell types naturally secrete as part of their tool kit for assimilating into new tissues.
However, I am less convinced in their ability to regenerate fully functional tissues in the synovium / cartilage, etc. on a large scale, or their ability to alter the underlying epigenetic damage that yields the auto-immune dynamic in the first place.
The reason for this has less to do with stem cell types, as it has to do with the diseased state of the tissue micro-environment that such transplanted cells will find themselves in.
Most biologic events in humans take place in “cellular communities” and both cell population, as well as the regulatory state of tissues is a critical factor here – (I recommend your readers familiarize themselves with a topic known as the “community effect”, originally termed by Sir John Gurdon)
The difference between the diseased human joint that stem cells are placed in, and the limb of the salamander that can be amputated only to regrow, is that ALL cell types in the micro-environment of the salamander limb re-model to assist in the re-development process and support the cell community to effect complete structure / function regeneration.
The micro-environment in the human joint remains in a fairly diseased state that doesn’t always support the new cell population very well – hence limiting true regeneration
However, in looking at the landscape of offerings in the DMARD (Disease-modifying anti-rheumatic drugs) segment, coupled with the side effects / toxicities of such existing products, stem cell options definitely have a role in the therapeutic space.
Q: You have an intensive pharmaceutical background. How are you integrating that background (assuming you are) into the work you are now doing on human regeneration, disease reversion and biologic age reversal?
A: My background over the past 25 years in pharma has taught me many things – some good (that we have the technology available to us today to really change the landscape of human health) and some not so good (that if we continue to follow the existing model, those advances will be indefinitely on the horizon).
I will try and sum it up in the following:
Since the inception of the modern pharmaceutical industry, researchers have attempted to reduce and study human health and disease at the level of their most basic components – proteins, genes, cells, etc. continually looking for new targets to develop drugs compounds for that can interfere in some fashion with biological processes.
In parallel, from the clinical perspective, patients have continued to be classified and studied in a very standardized fashion at the population level, primarily based on disease symptoms, via “gold standard” randomized clinical trials.
While these approaches have ultimately allowed the pharmaceutical industry to grow in size and profitability, giving us many treatments for disease, they have given us (with the sole exception of the antibiotic) very few cures for disease.
The primary reason for this is that innovation in the industry (as well as at the level of regulatory organizations) has fallen literally decades behind what the science is has been teaching us in the lab.
From the perspective of drug development, disciplines such as systems biology have shown us that the targets that traditional drugs are developed against are no more than the late-appearing indications of dysfunctional tissue / organ systems (i.e. symptoms of disease - inflammation, immunity, fibrosis, thrombosis, hemorrhage, cell proliferation, apoptosis, and necrosis), and that these drugs are being developed without regard for, or knowledge of, any biological factors that precede these abnormalities (causes of disease).
Additionally, the reductionist approach that is used to identify disease mechanisms or therapeutic targets continues to ignore the fact disease is rarely (if ever) a simple consequence of an abnormality in a single gene product, but rather, is an emergent state involving multiple biological processes that interact in complex networks.
Lastly, the disciplines of pharmacogenomics and toxicogenomics have continued to highlight that each of us are extremely different from each other in regard to the way drugs both benefit and/ or harm us.
Traditional “gold standard”, population level clinical studies continue to use definitions of disease that are excessively inclusive and are based on disease characterizations from decades ago. These inclusive definitions of disease not only obscure important differences among individuals with common clinical presentations, but also ignore underlying disease and / or toxicity mechanisms.
In summary, the traditional pharma approach of developing single target drugs based solely on disease symptoms, combined with clinical study models have ignored human / disease heterogeneity, have brought us to where we are today – lots of treatments; modest improvement in outcomes; no cures.
It is very difficult to get industry people (and for that matter even university folks) to think outside of this model due to it being the core dynamic within the pharma / life science private equity / FDA triad.
We hope to change a lot with our model at Bioquark.
Q: I am currently a pretty healthy 54 year old in good shape. I was thinking of HESC treatment perhaps in India from Dr. Geeta Shroff's clinic for health and longevity. Do you have any thoughts on this?
A: HESC’s are fascinating cells – no doubt about it – and they have gotten quite a bit of press over the past years based on their pluripotency and their plasticity for differentiation.
However, it is very important to keep in mind what cells can become in the petri dish, and what they can do in the human body, are two very different things.
Once again, I strongly advocate for studying medical research history, and a lot of the “forgotten” learnings:
The stem cells as “the fountain of youth” argument unfortunately violates a lot of the knowledge generated during the regenerative biology era (1940s-1970s) when thousands of publications occurred on “cross age transplantation” which definitively showed that old cells going into a young body micro-environment, did much better than young cells going into older body micro-environment – young cells for the most part acquired the aged phenotype of the tissue they were being placed into
So for the longevity question, the scientific community needs to come up with more than just the stem cell transplant concept
Sure - those stem cells can secrete youthful factors, but the numbers don’t add up when millions of young cells get placed into an environment with trillions of old ones. The “community effect” is strongly biased against them
Hence, this is why we think that the egg cell, which is responsible for “age reversal” in the first place, as well as being the stem cell creator, is where the answers for true rejuvenation will be found.
The bio-factors in a single egg have the ability to affect thousands of cells simultaneously. It’s not a 1-to-1 relationship.
Also, one must always keep in mind the problems that undifferentiated, pluripotent cells could pose if they are administered in a bolus format into a micro-environment that doesn’t support their appropriate differentiation and engraftment (i.e. teratoma formation)
Q: Patients are often lectured by those in the industry who are not medical doctors to be wary of stem cell clinics offering "unproven" treatments, especially those offshore. Isn't all medicine in its infancy unproven? Why do these fear mongers continue to ignore the thousands killed by FDA approved drugs and instead harp on about the great risks of stem cell therapy for which there is little proof of harm? The current clinical trial and regulatory approval process was developed around the risks/benefits of pharmaceutical drugs. Does this model fit the biologics and regenerative medicine era that is upon us? If not, what modifications do you think would be the best?
A: I would go beyond saying that “all medicine in its infancy is unproven” to “all medicine is unproven” Keep in mind that there are drugs that have been on the market for decades that we still have no idea how and/or why they work – most people would be surprised to find out how many FDA approved drugs in their approved labeling state: Mechanism Of Action -Unknown
Additionally, the widely acknowledged, but largely unspoken truths from the industry persist: all of the “disease output” targeted drugs that eventually make it to the market will only ever work in a small percentage of the target population they are approved for (due to our emerging knowledge of patient and disease heterogeneity)
The fear mongering is completely unwarranted: partially based on the obvious financial competing interests (pharma, life science PE, university R&D grant bodies, etc.); partially based on an isolation of thought processes.
Let’s go over history again - many of the greatest biomedical discoveries of all time, including penicillin, insulin, aspirin, opiates, smallpox vaccine, and quinine, just to name a few, happened in an era with minimal central regulatory oversight.
Insulin, as one bright historical example of the potential of unleashed and intelligent biomedical innovation, discovered in 1921, was on the market by 1923, benefiting patients around the world.
Unfortunately, a handful of negative events such as those surrounding Elixir Sulfanilamide in the 1930s, and later with Thalidomide in the 1950s (highlighting the importance of testing for acute toxicity and teratogenicity, respectively – quite easy to do nowadays), set in motion a chain reaction of hyper-regulatory dynamics in the ensuing decades that hasn’t slowed down since, all in the name of a bold, but un-reachable goal: long term safety.
From an approved drug perspective, today there are literally hundreds of FDA approved products on the market that can: prolong QT and/or Cause Torsades De Pointes resulting in sudden cardiac death; which are IARC Group 1 and 2 carcinogens; which have significant ”black boxed” SAE warnings, including “death” (not a nice one) – not to mention the sheer number of withdrawals, as well as adverse drug events (ADE) and deaths, associated with approved, marketed drugs (2 million ADE and 100,000 fatalities annually in U.S. alone) which have gone through decades of human testing and use, to realize that something is very wrong with the current regulatory gauntlet concept.
Animal models remain poorly predictive for humans, yet remain a mandatory cornerstone behind years and millions of dollars of early drug development activities. Penicillin kills guinea pigs and produces birth defects in rats, aspirin is poisonous to cats, cancer has been “cured in mice” thousands of times, and dozens of drugs found safe in animals are later withdrawn from market due to adverse drug events in humans.
Additionally, as mentioned previously we continue to spend billions of dollars on traditional “gold standard”, population level clinical studies, despite the fact that they use definitions of disease that are excessively inclusive (based upon disease characterizations from literally decades ago), while at the same time are excessively exclusive of major segments of the patient populace.
As a result, important differences among individuals with common clinical presentations are obscured, and we end up completely ignoring important underlying pharmacogenomic and toxicogenomic variability.
The more we learn, the more we realize that every patient’s disease is a rare disease!
Lastly, in an era of unprecedented biomedical discovery, patient access to “unproven interventions in clinical practice” (as defined and accepted by the 10+ million clinician members of the World Medical Association and their Declaration of Helsinki) has been severely limited in many developed nations and millions go to the grave annually without any fighting chance.
In our opinion, the overwhelming majority of patients and clinicians would happily accept a system of reduced regulatory burden in order to expedite life-saving therapeutic development and usage, and are advocates of the need for a parallel system for such “no option” patients to tap into.
One only needs to survey the landscape where such dynamics exist in “stealth mode” in current society to see where these concepts are already permeating our lives.
From a therapeutic perspective, current FDA initiatives regarding expanded access, off-label use, “animal rule only” development, and botanical drugs, as well as their public written position on personal importation, all highlight examples of various degrees of clinical, “let the patient beware” freedom that the agency is quietly willing to grant subjects today who seek out such products or who engage in related studies.
Further afield from pharmaceuticals, markets such as dietary supplements, cosmetics, processed ingredient foods/beverages, tobacco, legalized marijuana, and pesticide/herbicide usage, all technically represent large, uncontrolled clinical experiments on the general public, that we all are quite willing to accept today as personal choices.
As the global population becomes more educated and aware of their ability to impact their own health and wellness, without the need for a dominant central regulatory body always calling the shots, we believe such a parallel system will emerge and thrive.
And we may be on the cusp of it in 2015:
The emergence of such trends including: personalization of medicine on an “n-of-1” basis, adaptive clinical design, globalization of health care training, compassionate use legislative initiatives for experimental therapies, wider acceptance of complementary medical technologies, and the growth of international medical travel, all point in the direction of alternative paths for patients and clinicians to access the therapies of tomorrow, today.
Q: In same day stem cell therapy, like for orthopedics and joints, the patient's cells are extracted, centrifuged, then re-introduced. Why does this process make the cells go into healing mode after they are re-introduced?
A: Well….technically, that is not exactly what is happening – although it sounds good
Your body is actually a vast reservoir of different signaling languages – chemical, biologic, bio-electric, even bio-magentic (I suggest readers learn about such interesting topics as electrotaxis, galvanotaxis, chemotaxis, etc.)
It is these signals, that your body is constantly sending out, that guide and allow cells (endogenously produced or externally administered) to go into healing mode when they are re-introduced to the system.
In such a model, what is then happening biologically is known as paracrine “cross-talk” between host tissue and secreted factors from the “visiting” cell population
This biologic communication, received and processed by your existing cells genetic apparatus, is the primary form of communication that your cells use on a day-to-day basis to maintain health and fitness.
As a much grander example, unbeknownst to many, you develop cancer every day of your life.
When cell A undertakes a dangerous transformation, it is cell B, C, D, E, etc. in the immediate micro-environment of cell A, that either will nudge it back in line, or cause it to commit suicide.
All of this is mediated by such paracrine signaling within the community of cells
From a stem cell therapy perspective, it is the goal to introduce “healthier” cells into damaged micro-environments to effect such change and alter the diseased phenotype via such biologic mechanisms.
There is a caveat here though, which is why stem cells are not always the “single magic bullet” they are portrayed as – there can also exist negative signals from other tissues in the damaged micro-environment, like from fibroblasts in scar tissues, for instance, that do not care too much for new healthy cells coming into their territory, and they can give off inhibitory signals to thwart the newly arriving stem cells
Hence, your body, behind the scenes, becomes a very complex cellular battlefield.
Q: Will products/treatments for age reversal be so cost prohibitive that only the very rich will be able to afford them? At what age would reversal no longer be possible? I can't imagine someone in their 80's or 90's being able to reverse aging more than a few years at best.
A: This will hold true only if the old paradigm of developing single mechanism based drugs, against single biologic targets, is continued to be followed by the industry
In our opinion, it will not be the case if more creative, “heterogenic” approaches are employed.
For instance, the results seen in recent experiments with young blood being infused into older tissues (emulating parabiosis) is one example of an inexpensive, common sense approach that will not be very costly
Such an approach, where literally hundreds of biochemical factors present in younger blood are being administered to an older body, hence addressing multiple targets simultaneously, represents a novel paradigm shift.
The same goes with what we are doing at Bioquark with combinatorial biologics.
To date, in our own chronic toxicology experiments in rodents, we have seen a nice 70% life extension boost almost as a side effect.
In our opinion, aging is a disease, is multi-factorial, and must be addressed as such – and we will be able to get “more than a few years” if done correctly
Q: Your website says the first organ you will focus on is the kidney. I'm fine with that, but why is it that no companies seem to want to take on lung disease? The funding for lung disease research is miserly compared to other diseases. Is it too complicated or why aren't more companies/researchers interested in it? Lung disease is the 3rd leading cause of death in the U.S., 4th in the world.
A: We are actually very interested and focused on the lung and pulmonary disorders, and have a partner in South Africa working with us due to the tremendous toll that tuberculosis takes in that region.
I think hesitancy in the past has had more to do with the existing tools available, the ability to deliver certain types of therapies to the lung, the unique 3D (almost 4D architecture of the lung as it is constantly in motion), the unique immune components related to it, and so forth.
Q: Can you elaborate a bit on Bioquark's cosmetic and nutritional supplement products?
A: As a tangent off of our core research program in the area of combinatorial biologics from ooplasms, we have also spent a bit of our effort in studying members of the plant, marine, and fungal communities where such related dynamics exist, primarily in species that humans consume as food products today.
Our goal has been to similarly capture this natural synergistic “biochemical language” that plants, fungi, and other organisms use on a daily basis to modulate and maintain their fitness and protect themselves from environmental damage, and develop a new generation of scientifically standardized and validated bio-actives for wellness support and natural beautification.
Q: I am an advocate for faster access to autologous stem cell therapy. It seems like researchers want us to wait until they have developed the ultimate man-made induced pluripotent stems. While iPSC may be the only way to make some types of cells (retinal, dopaminergic) aren't mesenchymal cells the simplest, least expensive way to help the most patients across a broad range of problems?
I'm interested in your opinion, both scientific and from a bioethics perspective.
A: I have stated my position above in regard to ethics and the experimental angle.
Mesenchymal cells are indeed a simple, inexpensive therapeutic method to address a range of problems – and from our perspective the majority of that benefit comes from what these cells secrete – technically, there may even be an equal amount of promise in the secretions captures in the so called “conditioned media” that these cells live in in the lab, as opposed the cells themselves, which may make for another range of useful products in the future
Pluripotent cells are indeed more plastic in what they can become in a petri dish – but as previously mentioned, that is still a long way from what happens in the human body
Q: What do you see as the future benefit of regenerative medicine when it comes to longevity? Will societies be able adjust to extended, healthier lifespans?
A: Our position as a company is that longevity is purely a function of your cell’s “transcriptional regulatory states”
It is NOT a function of their genomic output, which is the core mantra of big pharma and many of those who believe aging in just about “wear and tear”
If that regulatory state can be altered from point B back to point A, you can technically become younger
This is how several species of hydrozoan species accomplish real time, whole body “age reversal” and what we believe the ultimate path humans will have to follow and emulate in order to achieve the same results
Will societies adjust? We think so
We are capable of so many wonderful things in 2015 – and while over-population is a scary concept, I think a world with healthier, more vibrant individuals, all participating, benefits everyone
If we focused a little less on social media and reality TV, and put a little more of our combined brain power to these tasks, there’s not much we can’t realize
Ira S. Pastor – Chief Executive Officer; Bioquark Inc. (www.bioquark.com) a unique life sciences company that is working on novel bio-products for human regeneration, disease reversion, and biologic age reversal
Mr. Pastor has over 25 years of experience across multiple sectors of the pharmaceutical industry including pharmaceutical commercialization, biotech drug development, managed care, distribution, OTC, and retail; Previously served as VP, Business Development for phyto-medicine development company Phytomedics Inc., raising $40 million of private equity, consummating over $50 million of licensing deals, and bringing lead auto-immune botanical drug candidate from discovery stage to Phase III development; Prior to that, employed by SmithKline Beecham Pharmaceuticals working in sales, marketing, and business strategy positions. Mr. Pastor has also served as Vice President of Corporate Development for the pharmacy benefit management company Prescription Delivery Systems (acquired by Cigna Health Insurance); MBA, Temple University; BS, Pharmacy, Rutgers University
Mission: To bring an end to many of the most devastating ailments associated with human disease, degeneration, and death.
Ira S. Pastor
CEO
Bioquark Inc.
pastor@bioquark.com
www.bioquark.com
Questions & Answers
Q: Could you explain in plain language what medical products BioQuark is pursuing; i.e. combinatorial biologics and bio-products for human regeneration? How is this approach to regenerative medicine different from stem cell therapy? Can this approach be synergistic to make our own stem cells work better? Or to curtail rogue cancer cells without harsher treatments like chemo and radiation? Will these be off-the-shelf medicines? Will they be less expensive than personalized cell therapy? And the biggest question from a patient perspective - how far away is this therapy(ies) from clinical trials and eventual access? What will be the first product developed and tested by Bioquark, Inc.?
A: Bioquark Inc. (www.bioquark.com) is focused on the development of novel peptide based biologics, with the goal of inducing natural, endogenous regeneration and tissue repair in human beings.
As some background to the Bioquark story:
We currently live on a planet with other organisms, that from a health and wellness perspective, are much further advanced than humans.
Many lower organisms can replace lost or damaged organs and tissues that are identical in structure and function to the original, effortlessly regenerating a wide variety of tissues, including spinal cords, limbs, hearts, eyes, and even parts of their brains. In a similar fashion, many of these same species possess fascinating skills for repairing and reversing cellular and genetic damage. Cancer, as an example, is found to be extremely rare in species displaying an efficient regenerative mechanism, even under the action of potent carcinogens. In many cases, when cancer does occur, tumors have been found to spontaneously remodel and integrate into their surroundings as normal, healthy tissue. Some of these organisms can even age, and then return to a youthful state later on in life. Needless to say, humans are pretty weak when it comes to accomplishing any of these feats.
What we discovered in the early days of Bioquark’s research program, was that these themes (what we call the 3 R’s - Regeneration, Reorganization, and Reanimation) were all intimately connected by an underlying capability in such organisms to 1) turn back biologic time in targeted tissues, and 2) start the development process over again. And while stem cells were a part of the process, there were many other important biologic forces at work simultaneously.
Hence Bioquark Inc. was formed with a goal of creating a single therapeutic platform, based on peptide therapeutics, which could help humans to mimic these abilities for purposes of health and wellness.
While these 3 dynamics are present in many different forms throughout nature and across species, in humans these abilities are found co-existing in the synergistic biochemical dynamics found within activated ooplasms (the cytoplasm of the egg following fertilization); hence Bioquark's program focuses on deriving novel biochemical materials from these ooplasms and applying them in human health.
We refer to these materials as “combinatorial biologics” because they represent NOT single drug entities, but defined, standardized mixtures of biologic materials (peptides, microRNA, etc.) that the egg uses to undertake the range of its very important responsibilities related to taking care of the new embryo which include: resetting cellular age, reprogramming DNA to eliminate genetic and epigenetic damage, remodeling of organelles, protection from inflammatory, oxidative, and infectious damage etc.
While ooplasm based reprogramming has been studied for the past 60 years in the petri dish in the forms of cloning, IVF, and most recently in the production of iPSC cells, Bioquark has decided instead of going in the direction of the stem cell model, to instead develop off-the-shelf biologics for direct therapeutic application in humans.
Hence our core product looks like any typical biologic drug material (insulin, interferon, etc.) , and will be administered via a range of traditional delivery vehicles SC, IM, intra-thecal, etc. depending on the target indication or tissue.
The egg is a very important cell as it is not only the “mother” cell of future stem cells, but it needs to fulfill a variety of support responsibilities until those stem cells are able to operate on their own. Hence we see a lot of synergy not only in direct therapeutic use of such biologics, in reprogramming diseased tissues to a healthier state, but also in the guidance of stem cells in more complex forms of regeneration, including those required in 3D organs and limbs.
While as a U.S. based biologics company we are still considered early stage from a traditional development perspective, we do have technology transfer licensees in other territories ex. U.S. that are more rapidly pursuing human clinical applications of our technologies, in territories with more conducive regulatory environments.
Q: What is your opinion of stem cells for the treatment of rheumatoid arthritis? What type of stem cells might work best and why?
A: I think that there may be some short term benefit in the anti-inflammatory / immuno-modulatory effects of the paracrine / trophic “cocktails”, that the various stem cell types naturally secrete as part of their tool kit for assimilating into new tissues.
However, I am less convinced in their ability to regenerate fully functional tissues in the synovium / cartilage, etc. on a large scale, or their ability to alter the underlying epigenetic damage that yields the auto-immune dynamic in the first place.
The reason for this has less to do with stem cell types, as it has to do with the diseased state of the tissue micro-environment that such transplanted cells will find themselves in.
Most biologic events in humans take place in “cellular communities” and both cell population, as well as the regulatory state of tissues is a critical factor here – (I recommend your readers familiarize themselves with a topic known as the “community effect”, originally termed by Sir John Gurdon)
The difference between the diseased human joint that stem cells are placed in, and the limb of the salamander that can be amputated only to regrow, is that ALL cell types in the micro-environment of the salamander limb re-model to assist in the re-development process and support the cell community to effect complete structure / function regeneration.
The micro-environment in the human joint remains in a fairly diseased state that doesn’t always support the new cell population very well – hence limiting true regeneration
However, in looking at the landscape of offerings in the DMARD (Disease-modifying anti-rheumatic drugs) segment, coupled with the side effects / toxicities of such existing products, stem cell options definitely have a role in the therapeutic space.
Q: You have an intensive pharmaceutical background. How are you integrating that background (assuming you are) into the work you are now doing on human regeneration, disease reversion and biologic age reversal?
A: My background over the past 25 years in pharma has taught me many things – some good (that we have the technology available to us today to really change the landscape of human health) and some not so good (that if we continue to follow the existing model, those advances will be indefinitely on the horizon).
I will try and sum it up in the following:
Since the inception of the modern pharmaceutical industry, researchers have attempted to reduce and study human health and disease at the level of their most basic components – proteins, genes, cells, etc. continually looking for new targets to develop drugs compounds for that can interfere in some fashion with biological processes.
In parallel, from the clinical perspective, patients have continued to be classified and studied in a very standardized fashion at the population level, primarily based on disease symptoms, via “gold standard” randomized clinical trials.
While these approaches have ultimately allowed the pharmaceutical industry to grow in size and profitability, giving us many treatments for disease, they have given us (with the sole exception of the antibiotic) very few cures for disease.
The primary reason for this is that innovation in the industry (as well as at the level of regulatory organizations) has fallen literally decades behind what the science is has been teaching us in the lab.
From the perspective of drug development, disciplines such as systems biology have shown us that the targets that traditional drugs are developed against are no more than the late-appearing indications of dysfunctional tissue / organ systems (i.e. symptoms of disease - inflammation, immunity, fibrosis, thrombosis, hemorrhage, cell proliferation, apoptosis, and necrosis), and that these drugs are being developed without regard for, or knowledge of, any biological factors that precede these abnormalities (causes of disease).
Additionally, the reductionist approach that is used to identify disease mechanisms or therapeutic targets continues to ignore the fact disease is rarely (if ever) a simple consequence of an abnormality in a single gene product, but rather, is an emergent state involving multiple biological processes that interact in complex networks.
Lastly, the disciplines of pharmacogenomics and toxicogenomics have continued to highlight that each of us are extremely different from each other in regard to the way drugs both benefit and/ or harm us.
Traditional “gold standard”, population level clinical studies continue to use definitions of disease that are excessively inclusive and are based on disease characterizations from decades ago. These inclusive definitions of disease not only obscure important differences among individuals with common clinical presentations, but also ignore underlying disease and / or toxicity mechanisms.
In summary, the traditional pharma approach of developing single target drugs based solely on disease symptoms, combined with clinical study models have ignored human / disease heterogeneity, have brought us to where we are today – lots of treatments; modest improvement in outcomes; no cures.
It is very difficult to get industry people (and for that matter even university folks) to think outside of this model due to it being the core dynamic within the pharma / life science private equity / FDA triad.
We hope to change a lot with our model at Bioquark.
Q: I am currently a pretty healthy 54 year old in good shape. I was thinking of HESC treatment perhaps in India from Dr. Geeta Shroff's clinic for health and longevity. Do you have any thoughts on this?
A: HESC’s are fascinating cells – no doubt about it – and they have gotten quite a bit of press over the past years based on their pluripotency and their plasticity for differentiation.
However, it is very important to keep in mind what cells can become in the petri dish, and what they can do in the human body, are two very different things.
Once again, I strongly advocate for studying medical research history, and a lot of the “forgotten” learnings:
The stem cells as “the fountain of youth” argument unfortunately violates a lot of the knowledge generated during the regenerative biology era (1940s-1970s) when thousands of publications occurred on “cross age transplantation” which definitively showed that old cells going into a young body micro-environment, did much better than young cells going into older body micro-environment – young cells for the most part acquired the aged phenotype of the tissue they were being placed into
So for the longevity question, the scientific community needs to come up with more than just the stem cell transplant concept
Sure - those stem cells can secrete youthful factors, but the numbers don’t add up when millions of young cells get placed into an environment with trillions of old ones. The “community effect” is strongly biased against them
Hence, this is why we think that the egg cell, which is responsible for “age reversal” in the first place, as well as being the stem cell creator, is where the answers for true rejuvenation will be found.
The bio-factors in a single egg have the ability to affect thousands of cells simultaneously. It’s not a 1-to-1 relationship.
Also, one must always keep in mind the problems that undifferentiated, pluripotent cells could pose if they are administered in a bolus format into a micro-environment that doesn’t support their appropriate differentiation and engraftment (i.e. teratoma formation)
Q: Patients are often lectured by those in the industry who are not medical doctors to be wary of stem cell clinics offering "unproven" treatments, especially those offshore. Isn't all medicine in its infancy unproven? Why do these fear mongers continue to ignore the thousands killed by FDA approved drugs and instead harp on about the great risks of stem cell therapy for which there is little proof of harm? The current clinical trial and regulatory approval process was developed around the risks/benefits of pharmaceutical drugs. Does this model fit the biologics and regenerative medicine era that is upon us? If not, what modifications do you think would be the best?
A: I would go beyond saying that “all medicine in its infancy is unproven” to “all medicine is unproven” Keep in mind that there are drugs that have been on the market for decades that we still have no idea how and/or why they work – most people would be surprised to find out how many FDA approved drugs in their approved labeling state: Mechanism Of Action -Unknown
Additionally, the widely acknowledged, but largely unspoken truths from the industry persist: all of the “disease output” targeted drugs that eventually make it to the market will only ever work in a small percentage of the target population they are approved for (due to our emerging knowledge of patient and disease heterogeneity)
The fear mongering is completely unwarranted: partially based on the obvious financial competing interests (pharma, life science PE, university R&D grant bodies, etc.); partially based on an isolation of thought processes.
Let’s go over history again - many of the greatest biomedical discoveries of all time, including penicillin, insulin, aspirin, opiates, smallpox vaccine, and quinine, just to name a few, happened in an era with minimal central regulatory oversight.
Insulin, as one bright historical example of the potential of unleashed and intelligent biomedical innovation, discovered in 1921, was on the market by 1923, benefiting patients around the world.
Unfortunately, a handful of negative events such as those surrounding Elixir Sulfanilamide in the 1930s, and later with Thalidomide in the 1950s (highlighting the importance of testing for acute toxicity and teratogenicity, respectively – quite easy to do nowadays), set in motion a chain reaction of hyper-regulatory dynamics in the ensuing decades that hasn’t slowed down since, all in the name of a bold, but un-reachable goal: long term safety.
From an approved drug perspective, today there are literally hundreds of FDA approved products on the market that can: prolong QT and/or Cause Torsades De Pointes resulting in sudden cardiac death; which are IARC Group 1 and 2 carcinogens; which have significant ”black boxed” SAE warnings, including “death” (not a nice one) – not to mention the sheer number of withdrawals, as well as adverse drug events (ADE) and deaths, associated with approved, marketed drugs (2 million ADE and 100,000 fatalities annually in U.S. alone) which have gone through decades of human testing and use, to realize that something is very wrong with the current regulatory gauntlet concept.
Animal models remain poorly predictive for humans, yet remain a mandatory cornerstone behind years and millions of dollars of early drug development activities. Penicillin kills guinea pigs and produces birth defects in rats, aspirin is poisonous to cats, cancer has been “cured in mice” thousands of times, and dozens of drugs found safe in animals are later withdrawn from market due to adverse drug events in humans.
Additionally, as mentioned previously we continue to spend billions of dollars on traditional “gold standard”, population level clinical studies, despite the fact that they use definitions of disease that are excessively inclusive (based upon disease characterizations from literally decades ago), while at the same time are excessively exclusive of major segments of the patient populace.
As a result, important differences among individuals with common clinical presentations are obscured, and we end up completely ignoring important underlying pharmacogenomic and toxicogenomic variability.
The more we learn, the more we realize that every patient’s disease is a rare disease!
Lastly, in an era of unprecedented biomedical discovery, patient access to “unproven interventions in clinical practice” (as defined and accepted by the 10+ million clinician members of the World Medical Association and their Declaration of Helsinki) has been severely limited in many developed nations and millions go to the grave annually without any fighting chance.
In our opinion, the overwhelming majority of patients and clinicians would happily accept a system of reduced regulatory burden in order to expedite life-saving therapeutic development and usage, and are advocates of the need for a parallel system for such “no option” patients to tap into.
One only needs to survey the landscape where such dynamics exist in “stealth mode” in current society to see where these concepts are already permeating our lives.
From a therapeutic perspective, current FDA initiatives regarding expanded access, off-label use, “animal rule only” development, and botanical drugs, as well as their public written position on personal importation, all highlight examples of various degrees of clinical, “let the patient beware” freedom that the agency is quietly willing to grant subjects today who seek out such products or who engage in related studies.
Further afield from pharmaceuticals, markets such as dietary supplements, cosmetics, processed ingredient foods/beverages, tobacco, legalized marijuana, and pesticide/herbicide usage, all technically represent large, uncontrolled clinical experiments on the general public, that we all are quite willing to accept today as personal choices.
As the global population becomes more educated and aware of their ability to impact their own health and wellness, without the need for a dominant central regulatory body always calling the shots, we believe such a parallel system will emerge and thrive.
And we may be on the cusp of it in 2015:
The emergence of such trends including: personalization of medicine on an “n-of-1” basis, adaptive clinical design, globalization of health care training, compassionate use legislative initiatives for experimental therapies, wider acceptance of complementary medical technologies, and the growth of international medical travel, all point in the direction of alternative paths for patients and clinicians to access the therapies of tomorrow, today.
Q: In same day stem cell therapy, like for orthopedics and joints, the patient's cells are extracted, centrifuged, then re-introduced. Why does this process make the cells go into healing mode after they are re-introduced?
A: Well….technically, that is not exactly what is happening – although it sounds good
Your body is actually a vast reservoir of different signaling languages – chemical, biologic, bio-electric, even bio-magentic (I suggest readers learn about such interesting topics as electrotaxis, galvanotaxis, chemotaxis, etc.)
It is these signals, that your body is constantly sending out, that guide and allow cells (endogenously produced or externally administered) to go into healing mode when they are re-introduced to the system.
In such a model, what is then happening biologically is known as paracrine “cross-talk” between host tissue and secreted factors from the “visiting” cell population
This biologic communication, received and processed by your existing cells genetic apparatus, is the primary form of communication that your cells use on a day-to-day basis to maintain health and fitness.
As a much grander example, unbeknownst to many, you develop cancer every day of your life.
When cell A undertakes a dangerous transformation, it is cell B, C, D, E, etc. in the immediate micro-environment of cell A, that either will nudge it back in line, or cause it to commit suicide.
All of this is mediated by such paracrine signaling within the community of cells
From a stem cell therapy perspective, it is the goal to introduce “healthier” cells into damaged micro-environments to effect such change and alter the diseased phenotype via such biologic mechanisms.
There is a caveat here though, which is why stem cells are not always the “single magic bullet” they are portrayed as – there can also exist negative signals from other tissues in the damaged micro-environment, like from fibroblasts in scar tissues, for instance, that do not care too much for new healthy cells coming into their territory, and they can give off inhibitory signals to thwart the newly arriving stem cells
Hence, your body, behind the scenes, becomes a very complex cellular battlefield.
Q: Will products/treatments for age reversal be so cost prohibitive that only the very rich will be able to afford them? At what age would reversal no longer be possible? I can't imagine someone in their 80's or 90's being able to reverse aging more than a few years at best.
A: This will hold true only if the old paradigm of developing single mechanism based drugs, against single biologic targets, is continued to be followed by the industry
In our opinion, it will not be the case if more creative, “heterogenic” approaches are employed.
For instance, the results seen in recent experiments with young blood being infused into older tissues (emulating parabiosis) is one example of an inexpensive, common sense approach that will not be very costly
Such an approach, where literally hundreds of biochemical factors present in younger blood are being administered to an older body, hence addressing multiple targets simultaneously, represents a novel paradigm shift.
The same goes with what we are doing at Bioquark with combinatorial biologics.
To date, in our own chronic toxicology experiments in rodents, we have seen a nice 70% life extension boost almost as a side effect.
In our opinion, aging is a disease, is multi-factorial, and must be addressed as such – and we will be able to get “more than a few years” if done correctly
Q: Your website says the first organ you will focus on is the kidney. I'm fine with that, but why is it that no companies seem to want to take on lung disease? The funding for lung disease research is miserly compared to other diseases. Is it too complicated or why aren't more companies/researchers interested in it? Lung disease is the 3rd leading cause of death in the U.S., 4th in the world.
A: We are actually very interested and focused on the lung and pulmonary disorders, and have a partner in South Africa working with us due to the tremendous toll that tuberculosis takes in that region.
I think hesitancy in the past has had more to do with the existing tools available, the ability to deliver certain types of therapies to the lung, the unique 3D (almost 4D architecture of the lung as it is constantly in motion), the unique immune components related to it, and so forth.
Q: Can you elaborate a bit on Bioquark's cosmetic and nutritional supplement products?
A: As a tangent off of our core research program in the area of combinatorial biologics from ooplasms, we have also spent a bit of our effort in studying members of the plant, marine, and fungal communities where such related dynamics exist, primarily in species that humans consume as food products today.
Our goal has been to similarly capture this natural synergistic “biochemical language” that plants, fungi, and other organisms use on a daily basis to modulate and maintain their fitness and protect themselves from environmental damage, and develop a new generation of scientifically standardized and validated bio-actives for wellness support and natural beautification.
Q: I am an advocate for faster access to autologous stem cell therapy. It seems like researchers want us to wait until they have developed the ultimate man-made induced pluripotent stems. While iPSC may be the only way to make some types of cells (retinal, dopaminergic) aren't mesenchymal cells the simplest, least expensive way to help the most patients across a broad range of problems?
I'm interested in your opinion, both scientific and from a bioethics perspective.
A: I have stated my position above in regard to ethics and the experimental angle.
Mesenchymal cells are indeed a simple, inexpensive therapeutic method to address a range of problems – and from our perspective the majority of that benefit comes from what these cells secrete – technically, there may even be an equal amount of promise in the secretions captures in the so called “conditioned media” that these cells live in in the lab, as opposed the cells themselves, which may make for another range of useful products in the future
Pluripotent cells are indeed more plastic in what they can become in a petri dish – but as previously mentioned, that is still a long way from what happens in the human body
Q: What do you see as the future benefit of regenerative medicine when it comes to longevity? Will societies be able adjust to extended, healthier lifespans?
A: Our position as a company is that longevity is purely a function of your cell’s “transcriptional regulatory states”
It is NOT a function of their genomic output, which is the core mantra of big pharma and many of those who believe aging in just about “wear and tear”
If that regulatory state can be altered from point B back to point A, you can technically become younger
This is how several species of hydrozoan species accomplish real time, whole body “age reversal” and what we believe the ultimate path humans will have to follow and emulate in order to achieve the same results
Will societies adjust? We think so
We are capable of so many wonderful things in 2015 – and while over-population is a scary concept, I think a world with healthier, more vibrant individuals, all participating, benefits everyone
If we focused a little less on social media and reality TV, and put a little more of our combined brain power to these tasks, there’s not much we can’t realize