About SiriCell Technologies
Thank you for inviting me to respond to a few of your readers' interesting questions.
To begin, let me explain that SiriCell Technologies's business model is designed to be an innovative and compliant therapeutic cell provider for patients that do not have the luxury of time to wait for the slow and politically charged process with the US FDA's approvals for cell therapies.
In no way are we now, or have we ever compromised best cell practices, or patient safety and have spent over two years and millions of dollars carefully working on our plans and preparation for a series of experimental and innovative clinical trials. The purpose of these trials is for the therapeutic benefit for those in real need and also to capture important clinical data to use for cell-based products to be conditionally approved, such as in a phase 4 model. Our hope is that this will eventually lead us to full commercial approvals in the countries we are working way ahead of the U.S.
The company has organized several foreign subsidiaries and established partnerships with leading strategic hospitals and other third party contributors in these select countries to initiate IRB approved, phase 1, 2 adaptive clinical trials. We feel that by managing our clinical trials outside of the U.S. we can move this along faster and for far less money than the conditions in the U.S. will presently allow.
The diseases we target are the classic "conditions without conventional hope" that the 21 CFR CEBR 601 regulations were designed for by the FDA. SiriCell will offer an opportunity to patients to take action now for their critical health needs, and partner in their own healthcare destiny with us. We have a clear vision for an internationally compliant and transparent clinical environment operating upon a management foundation based Compassionate Use Advocacy.
We do not advertise anywhere, but will keep our new website (under development) with accurate disclosures about our activities and with the clinical trial protocols posted for peer review and comment. We plan to share clinical data at predetermined milestones, as it matures, with additional information we feel should also be shared with the cell industry and public.
Additionally SiriCell is planning two clinical trials for elective and experimental treatments. One for next generation cosmetic cell-based treatments and a comprehensive trial on human aging and rejuvenation. Both conditions are not recognized as diseases by the U.S. FDA and can therefore not be formally approved in the classic sense. SiriCell anticipates this will change over the next few years as more evidence based data can be published and subsequently reconfirmed by others.
About Alex Moffett
I am a serial entrepreneur and have worked in life sciences for over 35 years. I have built a number of corporations around the world and have been based in Thailand for 16 years with my wife Cat, but we have had homes in several other countries as well.
Would best describe myself as an autodidact and have also been continuously educated by a growing number of friends, most of whom are M.D.s, and/or Ph.D.s. I have had a proclivity for sciences since a small child. I am the least important part of this company, it's story and our important goals for therapeutic cells. I consider myself a humble student of cell biology, epigenetics and translational cell therapies.
ALEX MOFFETT
Chairman & CEO
SiriCell Technologies, Inc.
539/29 Soi Sukhumvit, 31
Klong Tan Nua, Wattana,
Bangkok, Thailand 10110
Phone Numbers:
+668 343-99090 (Asia)
+1818 312-4027 (USA)
website: www.siricell.com
Q&A
Q: My son has cerebral palsy. He is seven years old. What is the best type of stem cell treatment for neurological brain injury for a child and what is the maximum amount of stem cells that you recommend? Is something like 200 million stem cells good or bad?
A: In relation to Cerebral Palsy (CP), the most important questions are which cell phenotypes to use and why? Secondly, how best to administer them to a patient? After this comes the decisions concerning the number of cells utilized in each transplant and then the best number of cellular transplants determined for a clinical trial and patient benefits. It is the opinion of SiriCell's expert advisory board that CP will require as series of cell treatments and that a one time administration of therapeutic cells will not be enough.
CP is an ischemic condition and there is a lot evidence already in the peer reviewed publications demonstrating that therapeutic cells clearly have the ability to repair and regenerate vascularization as might be required. So the 200 million cell number is not as important as the actual number of cells that can actually reach and effectively treat the areas of the bran affected. Obviously patient age and body weight are taken into consideration for each patient. Also the severity of the CP in the specific patient being treated. Plus the treatment must hopefully address the multifactorial disontogeny of CNS developing in CP. All very complicated to calculate at this point in our evolving understanding of this disease. This is why to advance this understanding a series of clinical trials with comparative arms and dose escalations must be performed in a responsible manner. There is no other way to properly identify the optimal "therapeutic sweet spot" required for maximum patient benefits.
Cerebral Palsy is one of the first conditions we are optimizing clinical trials to address and we will open an Expanded Access Program later on to complement our experimental and Adaptive Phase 1, 2 trials. This is true for many of the conditions we have plans for.
Many experts have suggested that the autologous MSC-like cells, or CD 34s from the peripheral blood might be good options for treatment. Others are still working on ESC, or IPS modified cell lines. But none of these choices allow for an accelerated path forward to the clinic and patient relief. SiriCell's strategies also consider the fact that any cell phenotypes that have crossed the transformative tissue fate line may produce unexpected complications once administered into the brain. This is also why FDA has argued for and established regulations namely 21 CFR HCT/Ps, Part 1271 361 for only homologous cell transplantation, without more than minimal manipulation in same day procedures. Any other cell products requires pre-market approval and we all know this does not happen fast.
When I was studying the clinical models in China they primarily utilized allogeneic, ex-vivo expanded cord blood mononuclear cells and bone marrow MSCs they were used experimentally under China's somewhat cloudy Class 3 Medical Treatment allowance. The doctors were able to see some degree of symptomatic relief in CP patients. But this benefit varied a lot. It seemed to me that for all I saw, or was told by the treating physicians, the earlier the patients were treated the better the results. So time and access to the cells is very important to capture the best clinical outcomes.
This was all far from perfect and most of the clinical activities were performed as the Practice of Medicine and not managed within the confines of well designed, managed and monitored clinical trials. So there were thousands of patients treated, in many different ways, and without appropriate transparency or sharing of key data via peer reviewed publications. This primary laps in good judgement by the hospitals, doctors and regulators there was one of the most unfortunate lost opportunities for the global cell therapy industry to learn from. What is important was that I learned everything they were doing, both right and wrong and then set out to improve the model in every way possible.
The good news is that although the early treatments were deficient in many ways, still patients could come and be involved in a cell trial if they were acceptable, were willing to pay and chose to do so. I have no doubt that whatever cell therapies are approved for clinical use now via the official regulatory pathway, or some of the fast tracks being promoted by say Korea and Japan, or the highly controversial practice of medicine in its varied forms, we will be utilizing better cell products in three to five more years. I expect this will keep changing for the better for several more decades to come. But what about those in serious need right now? Part of the answer we feel is what SiriCell is doing today.
Cell Delivery options for CP
The deliver of therapeutic cell to the brain raises many unique challenges. If 200 million cells are injected via an IV how can we control how many are caught in the lungs, liver and spleen during the "first pass" within the circulatory system. Well we can't and many cells do get stuck in these organs, or are attracted to other points of injury in the body via advanced forms of cell signaling. Next comes how to get them past the Blood Brain Barrier (BBB)?
Historically, this problem was first addressed in 1908 by Stereotactic surgical administration. This involved cutting the head open for an injection. Obviously highly invasive and dangerous. As technologies like radiography developed this became more controlled, but there were many problems that would always remain.
After this there were delivery protocols that utilized Mannitol, Alkylglycerol and other materials to temporarily open the BBB to allow for therapeutic delivery of various agents, but this, of course, is indiscriminate as to what gets into the brain.
SiriCell feels that a combinatorial therapeutic approach with cell administration is best. Systemic injections combined with Intranasal administration of the selected cells seems the most promising and would require far fewer cells, due to the ability to just let the cells migrate to where they are required without the first pass concerns reducing the number of cells and the highly targeted delivery. We have been strong supporters of this technological innovation and here I have added a good study for those that want to learn more from real experts on this subject:
Eur J Cell Biol. 2009 Jun;88(6):315-24. doi: 10.1016/j.ejcb.2009.02.001. Epub 2009 Mar 25.
Intranasal delivery of cells to the brain.
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Buadze M, Geisler J, Klopfer T, Burkhardt U, Proksch B, Verleysdonk S, Ayturan M, Buniatian GH, Gleiter CH,Frey WH 2nd.
Source
Department of Clinical Pharmacology, University Hospital of Tuebingen, Otfried-Mueller Str. 45, D-72076 Tuebingen, Germany. lusine.danielyan@med.uni-tuebingen.de
Abstract
The safety and efficacy of cell-based therapies for neurodegenerative diseases depends on the mode of cell administration. We hypothesized that intranasally administered cells could bypass the blood-brain barrier by migrating from the nasal mucosa through the cribriform plate along the olfactory neural pathway into the brain and cerebrospinal fluid (CSF). This would minimize or eliminate the distribution of cellular grafts to peripheral organs and will help to dispense with neurosurgical cell implantation. Here we demonstrate transnasal delivery of cells to the brain following intranasal application of fluorescently labeled rat mesenchymal stem cells (MSC) or human glioma cells to naive mice and rats. After cells crossed the cribriform plate, two migration routes were identified: (1) migration into the olfactory bulb and to other parts of the brain; (2) entry into the CSF with movement along the surface of the cortex followed by entrance into the brain parenchyma. The delivery of cells was enhanced by hyaluronidase treatment applied intranasally 30 min prior to the application of cells. Intranasal delivery provides a new non-invasive method for cell delivery to the CNS.
PMID:
19324456
[PubMed - indexed for MEDLINE]
In China they used IV and secondary injections into the subarachnoidal space via spinal puncture. Highly controversial as there is always risk of serious infections.
In addition to the cell phenotypes I mentioned above, we are also exploring some interesting new directions with even more primitive cell phenotypes that hold great promise in this regard. I will not go into great detail here due to the fact that this is work in progress, but all will soon be disclosed once our clinical trial protocol is finalized.
Q: There doesn't seem to be any doctors in the U.S. wanting to do stem cell research for ONH. Do you have any experience with this?
A: In China I watch a number of children be treated for their ONH and this was one of the conditions were we got IRB approval for in Malaysia. As I recall the Chinese treated over 60 ONH children and got some well publicized great results. Going from sightless to some vision was a medical impossibility only a decade ago. We watched it happen over and over.
The treatment protocol for this condition would use the same administrative approach and might add localized injections near the optic nerve as well. Many experts theorized that in addition to regenerating the optic nerve that the cells work effectively on the micro vasculature surrounding the nerve and this was useful as well. We are interested in this condition and are seeking more input from various ocular experts on this rather rare, but important condition. But I will add that this was one of the diseases that demonstrated significant tangible improvement for a condition without hope from any other therapeutic option available other than cell therapy. Still, we have a long way to go and this is why we are organizing more trials.
Q: I noticed that on your website, some of your advisory board members are well known for their life extension, anti-aging research. Is your company actively involved in this type of research? I assume stem cells are a big part of this research, but what else might hold promise to extend life expectancy and make aging something that doesn't debilitate one's mind and body?
A: Yes, SiriCell is primairly focused on Anti-Ageing technologies and the mechanisms from several cell candidates or their secretory gifts might add. These can be studied via a large number of biomarkers that we now have good technologies to monitor and compare at certain stages. We have known for many years now that by treating aging we would really be treating a plethora of age related diseases. And, most importantly, finally addressing the ultimate disease of humankind that I believe can and will be cured in this century - death.
There have been several important disclosures so far this year on this subject that are rocking the minds of cell scientists everywhere. Some of the newly elucidated blood proteins, cell and gene activators are pushing our understand of epigenetic modulation and reversal. New understanding and revelations on the Chromatin Signatures and epigenetic phases of cell aging and the telomere-centric mechanisms are leading all this and keeping me and my associates up at night. Needless to say, we have a number of exciting ideas to pursue clinically and a clinical trial for those that want to partner in this exploratory adventure in human biology will be able to probably later this year. That's all I can say at this time, but you will all be hearing much more very soon.
Q: Anything new in the way of treatment for lung disease?
A: Yes, COPD and the related conditions are on the top of our list of conditions. I have a close first cousin named Gene who is fighting the clock right now in the advanced stages of COPD and this motivates me on a very personal level. He writes to me from time to time to simply ask me the same question, when can I come? You all know it's tied to working capital to expand the scope of our trials and move forward toward differentiation in the conditions we can work on. Perhaps you might realize it's been extremely difficult to fund this company and it's consumed a lot of my personal funds and that of my close friends and investors. I am working on this very issue right now which is why I have to keep my answers brief. We hope to be able to increase the number of trial centers so we can perform our trials in more locations and keep moving forward toward other life threatening conditions using our same business model.
We have some promising undervalued cells for this condition too and want to add concomitant cell nebulization to the standard forms of administration for the cells.
Q: What is the Facell treatment? Is it invasive and is there downtime? Does it need to be repeated at certain intervals and is it expensive?
A: The FaCell™ is one of the first international cell therapy cosmetic brands and this is our symbol for a series of evolving technologies designed to actually rejuvenate the dermal matrix on multiple synergistic levels. My goal is to move the market from Botox™ and it's shallow mechanisms of action as a toxin toward capturing the power of human biology and redirecting it in beneficial ways to serve us.
Naturally we are working with cell phenotypes and select secretory products from the cells, in addition to the TCF3 and TCF4 proteins and specific gene activations. We know that our skin ages from both chronological aging and photo aging. The concept is to inject an allogeneic cell and 2nd agent complex into the skin in a pattern that reached the right spots for the activation goals we have identified. We use expanded cells so we can count, characterize and control purity and viability, every time. If a cell therapy product is not standardized it can never be properly evaluated, nor commercialized.
A combination of cell phenotypes are also required for optimal results. So for both reasons stated, we will not be able to offer these facial injections in the U.S. for some time. For now people will need to fly outside of the U.S. for the treatments. SiriCell is organizing a subsidiary in the Bahamas and this in not so far away, or expensive to get there. The treatments will take two hours on an out-patient basis and a couple days of recovery, as some swelling would be natural. What a beautiful place to do something like this over a long weekend. We will present far more proof than the standard before and after pictures that never really match each other for a true comparison.
This cost now will be about $6,000 and we hope this can come down over time. I would expect people will do this one or twice per year and then watch the results. There will be some individual differences in the response which is true for many forms of aging and also how old one is when they get started will factor in a great deal.
Ever think about using cells as a prophylactic for a disease?, way before we hit the actual disease stage. It's going to happen and there will be a lot of screaming about the concept, but wellness is always about prevention, not reaction to a disease. That's just not a smart way to manage all this. But this is a fascinating conversation for another time.
Initially the FaCell™ will only be available in a clinical trial. And this will present many new challenges because its an elective procedure, but there are several clinical trials and FDA approvals that have set a precedent for an IRB approval. This is far more advanced than the SVF injections that the FDA has taken issue with in the U.S.
Q: Would a treatment with a large volume of stem cells administered once, be better than several treatments with smaller amounts of stem cells or is this something that depends on the type of stem cells and the disease one has or is this just a stupid question?
A: I was told long ago, "there are no unfair questions, only unfair answers." Well, I would say the answer to this question depends on many factors. A blood transfusion is a good example where you need a large amount of cells to do the trick. Where in balance an intranasal injection of cells would not require anywhere near the same numbers. I feel targeted delivery of cells will become progressively more important and common place. If one is utilizing a micro-catheter far less cells are logically required.
I have witnessed the power of serial injections of cells and there are many mechanisms of action at play in the cell therapies and often cell engraftment has nothing to do with the clinical efficacy. This all arose from the early years and initial clinical Hematopoietic procedures where HLA matching and cell engraftment were the primary targeted activities. We know that paracrine and autocrine stimulation is contributive to many cell therapies. We have studied what I call "Paracrine Pulse Protocols" where the repeated stimulation of the environment has produced better clinical results.
Q: I noticed that you use intranasal stem cell delivery rather than intrathecal injections through lumbar puncture. Your website says this method delivers much higher doses - how so?
A: The intrathecal injections are difficult to calculate on a patient by patient basis. So this is more of the medical art, rather than medical science and takes special skills and of course experience. Some of the doctors in China were very adept at this because they worked with severely spastic patients. As I mentioned above, there is a chance of series infections if this done incorrectly. Also the amount of spinal fluid that needs to be first removed before you can inject the cell payload back in can cause problems. This spinal fluid changes several times per day and the nerve can float around as the patient moves. Too much pressure resulting from the wrong amount of cells and carrier can cause bad headaches and other potentially more serious side effects. There is always a small chance of injuring the spinal cord too.
The other issue is that once you take some fluid out and add the cells in a delivery base, the cells have to navigate into the brain and there could only be a small amount of cells that could do so. Intranasal is far better and we will be using this in a number of trials and I can provide much better answers in a few years on this subject. We need the clinical data in hand that is solid before we can move to the next step. But it's very exciting and will open new doors in treating many of the diseases the industry is working on and you know them; CP, Parkinson's, Alzheimer's, TBI, Ataxia, Stroke, Autism and one day ALS. And let's not forget age related dementia...
Q: Are you doing any treatments for hearing loss in children or adults? If not, do you feel it is something that can be helped with stem cells in the future?
A: No, not now. We have heard of testimonials where this was a positive side effect from other treatments, but it's too early to talk about in my opinion. The good news is this technology is moving faster that almost anything I have ever studied. So in time many things will be possible. Stay positive and trust human biology, it's far more intelligent than any of us will ever be. The bottom line is many things that have always been impossible are now changing before our eyes. Stem cell technologies will transform health care forever and it's already begun.
Q: What does your treatment for MS consist of?
A: This is still in development and we are considering a number of patent opportunities, so I can not share more. But my Sister-in-law is suffering from MS and its on our radar for sure. We just want to use the best cells possible and we are monitoring a number of companies doing good work on this condition. Again, it's money that is required to move it all faster and in more directions.
Q: Do you have plans to open a clinic in the U.S.?
A: No, we do not right now. But we know that many of the trials we are organizing will be able to be used for FDA approvals later on. I explained before that our priority is treatments ASAP and the U.S. is not the easiest place to accomplish this goal. I am afraid we will watch many more companies trying to constantly raise money to play the antiquated approval game and most will drop out at phase 3. The finance people need a ROI and the cost of money keeps growing. We all know Geron gave up for many good business reasons after getting lots of capital, some really smart people on board and even CIRM loans! I feel we have a much better plan and it takes many individuals to properly support it. There is no dream without a team. It's time for patients to take a more proactive role and we want to help.
Q: I have a friend confined to a nursing home in the Philippines who has no funds for treatment for her COPD. Do you ever have any clinical trials or angel treatments that she could participate in? Her circumstances are dire as no one seems to even be able to help her obtain a portable oxygen unit.
A: We are planning a COPD clinical trial in Manila and you can contact me via email: amoffett@siricell.com
Closing Remarks from Alex Moffett
Thank you for the opportunity to share a little about what SiriCell is doing and why. After witnessing so much in China before, and connecting with the hundreds of patients I personally met there, plus the impact what I observed had on me, we are determined to build a patient-centric innovative and compliant business model for Adult Cell Therapies. An opportunity for those who cannot wait to receive clinically certified grade cells and to be able to do so in sophisticated clinical trials, managed by compassionately guided professionals who care more about delivering patient benefits rather than money. I cannot guarantee we will be able to do all that has been envisioned, but I know we all work constantly to make this happened. And as I often say to those that will actually listen, "The only real failure is not to try."
Sincerely,
Alex Moffett, CEO
Thank you for inviting me to respond to a few of your readers' interesting questions.
To begin, let me explain that SiriCell Technologies's business model is designed to be an innovative and compliant therapeutic cell provider for patients that do not have the luxury of time to wait for the slow and politically charged process with the US FDA's approvals for cell therapies.
In no way are we now, or have we ever compromised best cell practices, or patient safety and have spent over two years and millions of dollars carefully working on our plans and preparation for a series of experimental and innovative clinical trials. The purpose of these trials is for the therapeutic benefit for those in real need and also to capture important clinical data to use for cell-based products to be conditionally approved, such as in a phase 4 model. Our hope is that this will eventually lead us to full commercial approvals in the countries we are working way ahead of the U.S.
The company has organized several foreign subsidiaries and established partnerships with leading strategic hospitals and other third party contributors in these select countries to initiate IRB approved, phase 1, 2 adaptive clinical trials. We feel that by managing our clinical trials outside of the U.S. we can move this along faster and for far less money than the conditions in the U.S. will presently allow.
The diseases we target are the classic "conditions without conventional hope" that the 21 CFR CEBR 601 regulations were designed for by the FDA. SiriCell will offer an opportunity to patients to take action now for their critical health needs, and partner in their own healthcare destiny with us. We have a clear vision for an internationally compliant and transparent clinical environment operating upon a management foundation based Compassionate Use Advocacy.
We do not advertise anywhere, but will keep our new website (under development) with accurate disclosures about our activities and with the clinical trial protocols posted for peer review and comment. We plan to share clinical data at predetermined milestones, as it matures, with additional information we feel should also be shared with the cell industry and public.
Additionally SiriCell is planning two clinical trials for elective and experimental treatments. One for next generation cosmetic cell-based treatments and a comprehensive trial on human aging and rejuvenation. Both conditions are not recognized as diseases by the U.S. FDA and can therefore not be formally approved in the classic sense. SiriCell anticipates this will change over the next few years as more evidence based data can be published and subsequently reconfirmed by others.
About Alex Moffett
I am a serial entrepreneur and have worked in life sciences for over 35 years. I have built a number of corporations around the world and have been based in Thailand for 16 years with my wife Cat, but we have had homes in several other countries as well.
Would best describe myself as an autodidact and have also been continuously educated by a growing number of friends, most of whom are M.D.s, and/or Ph.D.s. I have had a proclivity for sciences since a small child. I am the least important part of this company, it's story and our important goals for therapeutic cells. I consider myself a humble student of cell biology, epigenetics and translational cell therapies.
ALEX MOFFETT
Chairman & CEO
SiriCell Technologies, Inc.
539/29 Soi Sukhumvit, 31
Klong Tan Nua, Wattana,
Bangkok, Thailand 10110
Phone Numbers:
+668 343-99090 (Asia)
+1818 312-4027 (USA)
website: www.siricell.com
Q&A
Q: My son has cerebral palsy. He is seven years old. What is the best type of stem cell treatment for neurological brain injury for a child and what is the maximum amount of stem cells that you recommend? Is something like 200 million stem cells good or bad?
A: In relation to Cerebral Palsy (CP), the most important questions are which cell phenotypes to use and why? Secondly, how best to administer them to a patient? After this comes the decisions concerning the number of cells utilized in each transplant and then the best number of cellular transplants determined for a clinical trial and patient benefits. It is the opinion of SiriCell's expert advisory board that CP will require as series of cell treatments and that a one time administration of therapeutic cells will not be enough.
CP is an ischemic condition and there is a lot evidence already in the peer reviewed publications demonstrating that therapeutic cells clearly have the ability to repair and regenerate vascularization as might be required. So the 200 million cell number is not as important as the actual number of cells that can actually reach and effectively treat the areas of the bran affected. Obviously patient age and body weight are taken into consideration for each patient. Also the severity of the CP in the specific patient being treated. Plus the treatment must hopefully address the multifactorial disontogeny of CNS developing in CP. All very complicated to calculate at this point in our evolving understanding of this disease. This is why to advance this understanding a series of clinical trials with comparative arms and dose escalations must be performed in a responsible manner. There is no other way to properly identify the optimal "therapeutic sweet spot" required for maximum patient benefits.
Cerebral Palsy is one of the first conditions we are optimizing clinical trials to address and we will open an Expanded Access Program later on to complement our experimental and Adaptive Phase 1, 2 trials. This is true for many of the conditions we have plans for.
Many experts have suggested that the autologous MSC-like cells, or CD 34s from the peripheral blood might be good options for treatment. Others are still working on ESC, or IPS modified cell lines. But none of these choices allow for an accelerated path forward to the clinic and patient relief. SiriCell's strategies also consider the fact that any cell phenotypes that have crossed the transformative tissue fate line may produce unexpected complications once administered into the brain. This is also why FDA has argued for and established regulations namely 21 CFR HCT/Ps, Part 1271 361 for only homologous cell transplantation, without more than minimal manipulation in same day procedures. Any other cell products requires pre-market approval and we all know this does not happen fast.
When I was studying the clinical models in China they primarily utilized allogeneic, ex-vivo expanded cord blood mononuclear cells and bone marrow MSCs they were used experimentally under China's somewhat cloudy Class 3 Medical Treatment allowance. The doctors were able to see some degree of symptomatic relief in CP patients. But this benefit varied a lot. It seemed to me that for all I saw, or was told by the treating physicians, the earlier the patients were treated the better the results. So time and access to the cells is very important to capture the best clinical outcomes.
This was all far from perfect and most of the clinical activities were performed as the Practice of Medicine and not managed within the confines of well designed, managed and monitored clinical trials. So there were thousands of patients treated, in many different ways, and without appropriate transparency or sharing of key data via peer reviewed publications. This primary laps in good judgement by the hospitals, doctors and regulators there was one of the most unfortunate lost opportunities for the global cell therapy industry to learn from. What is important was that I learned everything they were doing, both right and wrong and then set out to improve the model in every way possible.
The good news is that although the early treatments were deficient in many ways, still patients could come and be involved in a cell trial if they were acceptable, were willing to pay and chose to do so. I have no doubt that whatever cell therapies are approved for clinical use now via the official regulatory pathway, or some of the fast tracks being promoted by say Korea and Japan, or the highly controversial practice of medicine in its varied forms, we will be utilizing better cell products in three to five more years. I expect this will keep changing for the better for several more decades to come. But what about those in serious need right now? Part of the answer we feel is what SiriCell is doing today.
Cell Delivery options for CP
The deliver of therapeutic cell to the brain raises many unique challenges. If 200 million cells are injected via an IV how can we control how many are caught in the lungs, liver and spleen during the "first pass" within the circulatory system. Well we can't and many cells do get stuck in these organs, or are attracted to other points of injury in the body via advanced forms of cell signaling. Next comes how to get them past the Blood Brain Barrier (BBB)?
Historically, this problem was first addressed in 1908 by Stereotactic surgical administration. This involved cutting the head open for an injection. Obviously highly invasive and dangerous. As technologies like radiography developed this became more controlled, but there were many problems that would always remain.
After this there were delivery protocols that utilized Mannitol, Alkylglycerol and other materials to temporarily open the BBB to allow for therapeutic delivery of various agents, but this, of course, is indiscriminate as to what gets into the brain.
SiriCell feels that a combinatorial therapeutic approach with cell administration is best. Systemic injections combined with Intranasal administration of the selected cells seems the most promising and would require far fewer cells, due to the ability to just let the cells migrate to where they are required without the first pass concerns reducing the number of cells and the highly targeted delivery. We have been strong supporters of this technological innovation and here I have added a good study for those that want to learn more from real experts on this subject:
Eur J Cell Biol. 2009 Jun;88(6):315-24. doi: 10.1016/j.ejcb.2009.02.001. Epub 2009 Mar 25.
Intranasal delivery of cells to the brain.
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Buadze M, Geisler J, Klopfer T, Burkhardt U, Proksch B, Verleysdonk S, Ayturan M, Buniatian GH, Gleiter CH,Frey WH 2nd.
Source
Department of Clinical Pharmacology, University Hospital of Tuebingen, Otfried-Mueller Str. 45, D-72076 Tuebingen, Germany. lusine.danielyan@med.uni-tuebingen.de
Abstract
The safety and efficacy of cell-based therapies for neurodegenerative diseases depends on the mode of cell administration. We hypothesized that intranasally administered cells could bypass the blood-brain barrier by migrating from the nasal mucosa through the cribriform plate along the olfactory neural pathway into the brain and cerebrospinal fluid (CSF). This would minimize or eliminate the distribution of cellular grafts to peripheral organs and will help to dispense with neurosurgical cell implantation. Here we demonstrate transnasal delivery of cells to the brain following intranasal application of fluorescently labeled rat mesenchymal stem cells (MSC) or human glioma cells to naive mice and rats. After cells crossed the cribriform plate, two migration routes were identified: (1) migration into the olfactory bulb and to other parts of the brain; (2) entry into the CSF with movement along the surface of the cortex followed by entrance into the brain parenchyma. The delivery of cells was enhanced by hyaluronidase treatment applied intranasally 30 min prior to the application of cells. Intranasal delivery provides a new non-invasive method for cell delivery to the CNS.
PMID:
19324456
[PubMed - indexed for MEDLINE]
In China they used IV and secondary injections into the subarachnoidal space via spinal puncture. Highly controversial as there is always risk of serious infections.
In addition to the cell phenotypes I mentioned above, we are also exploring some interesting new directions with even more primitive cell phenotypes that hold great promise in this regard. I will not go into great detail here due to the fact that this is work in progress, but all will soon be disclosed once our clinical trial protocol is finalized.
Q: There doesn't seem to be any doctors in the U.S. wanting to do stem cell research for ONH. Do you have any experience with this?
A: In China I watch a number of children be treated for their ONH and this was one of the conditions were we got IRB approval for in Malaysia. As I recall the Chinese treated over 60 ONH children and got some well publicized great results. Going from sightless to some vision was a medical impossibility only a decade ago. We watched it happen over and over.
The treatment protocol for this condition would use the same administrative approach and might add localized injections near the optic nerve as well. Many experts theorized that in addition to regenerating the optic nerve that the cells work effectively on the micro vasculature surrounding the nerve and this was useful as well. We are interested in this condition and are seeking more input from various ocular experts on this rather rare, but important condition. But I will add that this was one of the diseases that demonstrated significant tangible improvement for a condition without hope from any other therapeutic option available other than cell therapy. Still, we have a long way to go and this is why we are organizing more trials.
Q: I noticed that on your website, some of your advisory board members are well known for their life extension, anti-aging research. Is your company actively involved in this type of research? I assume stem cells are a big part of this research, but what else might hold promise to extend life expectancy and make aging something that doesn't debilitate one's mind and body?
A: Yes, SiriCell is primairly focused on Anti-Ageing technologies and the mechanisms from several cell candidates or their secretory gifts might add. These can be studied via a large number of biomarkers that we now have good technologies to monitor and compare at certain stages. We have known for many years now that by treating aging we would really be treating a plethora of age related diseases. And, most importantly, finally addressing the ultimate disease of humankind that I believe can and will be cured in this century - death.
There have been several important disclosures so far this year on this subject that are rocking the minds of cell scientists everywhere. Some of the newly elucidated blood proteins, cell and gene activators are pushing our understand of epigenetic modulation and reversal. New understanding and revelations on the Chromatin Signatures and epigenetic phases of cell aging and the telomere-centric mechanisms are leading all this and keeping me and my associates up at night. Needless to say, we have a number of exciting ideas to pursue clinically and a clinical trial for those that want to partner in this exploratory adventure in human biology will be able to probably later this year. That's all I can say at this time, but you will all be hearing much more very soon.
Q: Anything new in the way of treatment for lung disease?
A: Yes, COPD and the related conditions are on the top of our list of conditions. I have a close first cousin named Gene who is fighting the clock right now in the advanced stages of COPD and this motivates me on a very personal level. He writes to me from time to time to simply ask me the same question, when can I come? You all know it's tied to working capital to expand the scope of our trials and move forward toward differentiation in the conditions we can work on. Perhaps you might realize it's been extremely difficult to fund this company and it's consumed a lot of my personal funds and that of my close friends and investors. I am working on this very issue right now which is why I have to keep my answers brief. We hope to be able to increase the number of trial centers so we can perform our trials in more locations and keep moving forward toward other life threatening conditions using our same business model.
We have some promising undervalued cells for this condition too and want to add concomitant cell nebulization to the standard forms of administration for the cells.
Q: What is the Facell treatment? Is it invasive and is there downtime? Does it need to be repeated at certain intervals and is it expensive?
A: The FaCell™ is one of the first international cell therapy cosmetic brands and this is our symbol for a series of evolving technologies designed to actually rejuvenate the dermal matrix on multiple synergistic levels. My goal is to move the market from Botox™ and it's shallow mechanisms of action as a toxin toward capturing the power of human biology and redirecting it in beneficial ways to serve us.
Naturally we are working with cell phenotypes and select secretory products from the cells, in addition to the TCF3 and TCF4 proteins and specific gene activations. We know that our skin ages from both chronological aging and photo aging. The concept is to inject an allogeneic cell and 2nd agent complex into the skin in a pattern that reached the right spots for the activation goals we have identified. We use expanded cells so we can count, characterize and control purity and viability, every time. If a cell therapy product is not standardized it can never be properly evaluated, nor commercialized.
A combination of cell phenotypes are also required for optimal results. So for both reasons stated, we will not be able to offer these facial injections in the U.S. for some time. For now people will need to fly outside of the U.S. for the treatments. SiriCell is organizing a subsidiary in the Bahamas and this in not so far away, or expensive to get there. The treatments will take two hours on an out-patient basis and a couple days of recovery, as some swelling would be natural. What a beautiful place to do something like this over a long weekend. We will present far more proof than the standard before and after pictures that never really match each other for a true comparison.
This cost now will be about $6,000 and we hope this can come down over time. I would expect people will do this one or twice per year and then watch the results. There will be some individual differences in the response which is true for many forms of aging and also how old one is when they get started will factor in a great deal.
Ever think about using cells as a prophylactic for a disease?, way before we hit the actual disease stage. It's going to happen and there will be a lot of screaming about the concept, but wellness is always about prevention, not reaction to a disease. That's just not a smart way to manage all this. But this is a fascinating conversation for another time.
Initially the FaCell™ will only be available in a clinical trial. And this will present many new challenges because its an elective procedure, but there are several clinical trials and FDA approvals that have set a precedent for an IRB approval. This is far more advanced than the SVF injections that the FDA has taken issue with in the U.S.
Q: Would a treatment with a large volume of stem cells administered once, be better than several treatments with smaller amounts of stem cells or is this something that depends on the type of stem cells and the disease one has or is this just a stupid question?
A: I was told long ago, "there are no unfair questions, only unfair answers." Well, I would say the answer to this question depends on many factors. A blood transfusion is a good example where you need a large amount of cells to do the trick. Where in balance an intranasal injection of cells would not require anywhere near the same numbers. I feel targeted delivery of cells will become progressively more important and common place. If one is utilizing a micro-catheter far less cells are logically required.
I have witnessed the power of serial injections of cells and there are many mechanisms of action at play in the cell therapies and often cell engraftment has nothing to do with the clinical efficacy. This all arose from the early years and initial clinical Hematopoietic procedures where HLA matching and cell engraftment were the primary targeted activities. We know that paracrine and autocrine stimulation is contributive to many cell therapies. We have studied what I call "Paracrine Pulse Protocols" where the repeated stimulation of the environment has produced better clinical results.
Q: I noticed that you use intranasal stem cell delivery rather than intrathecal injections through lumbar puncture. Your website says this method delivers much higher doses - how so?
A: The intrathecal injections are difficult to calculate on a patient by patient basis. So this is more of the medical art, rather than medical science and takes special skills and of course experience. Some of the doctors in China were very adept at this because they worked with severely spastic patients. As I mentioned above, there is a chance of series infections if this done incorrectly. Also the amount of spinal fluid that needs to be first removed before you can inject the cell payload back in can cause problems. This spinal fluid changes several times per day and the nerve can float around as the patient moves. Too much pressure resulting from the wrong amount of cells and carrier can cause bad headaches and other potentially more serious side effects. There is always a small chance of injuring the spinal cord too.
The other issue is that once you take some fluid out and add the cells in a delivery base, the cells have to navigate into the brain and there could only be a small amount of cells that could do so. Intranasal is far better and we will be using this in a number of trials and I can provide much better answers in a few years on this subject. We need the clinical data in hand that is solid before we can move to the next step. But it's very exciting and will open new doors in treating many of the diseases the industry is working on and you know them; CP, Parkinson's, Alzheimer's, TBI, Ataxia, Stroke, Autism and one day ALS. And let's not forget age related dementia...
Q: Are you doing any treatments for hearing loss in children or adults? If not, do you feel it is something that can be helped with stem cells in the future?
A: No, not now. We have heard of testimonials where this was a positive side effect from other treatments, but it's too early to talk about in my opinion. The good news is this technology is moving faster that almost anything I have ever studied. So in time many things will be possible. Stay positive and trust human biology, it's far more intelligent than any of us will ever be. The bottom line is many things that have always been impossible are now changing before our eyes. Stem cell technologies will transform health care forever and it's already begun.
Q: What does your treatment for MS consist of?
A: This is still in development and we are considering a number of patent opportunities, so I can not share more. But my Sister-in-law is suffering from MS and its on our radar for sure. We just want to use the best cells possible and we are monitoring a number of companies doing good work on this condition. Again, it's money that is required to move it all faster and in more directions.
Q: Do you have plans to open a clinic in the U.S.?
A: No, we do not right now. But we know that many of the trials we are organizing will be able to be used for FDA approvals later on. I explained before that our priority is treatments ASAP and the U.S. is not the easiest place to accomplish this goal. I am afraid we will watch many more companies trying to constantly raise money to play the antiquated approval game and most will drop out at phase 3. The finance people need a ROI and the cost of money keeps growing. We all know Geron gave up for many good business reasons after getting lots of capital, some really smart people on board and even CIRM loans! I feel we have a much better plan and it takes many individuals to properly support it. There is no dream without a team. It's time for patients to take a more proactive role and we want to help.
Q: I have a friend confined to a nursing home in the Philippines who has no funds for treatment for her COPD. Do you ever have any clinical trials or angel treatments that she could participate in? Her circumstances are dire as no one seems to even be able to help her obtain a portable oxygen unit.
A: We are planning a COPD clinical trial in Manila and you can contact me via email: amoffett@siricell.com
Closing Remarks from Alex Moffett
Thank you for the opportunity to share a little about what SiriCell is doing and why. After witnessing so much in China before, and connecting with the hundreds of patients I personally met there, plus the impact what I observed had on me, we are determined to build a patient-centric innovative and compliant business model for Adult Cell Therapies. An opportunity for those who cannot wait to receive clinically certified grade cells and to be able to do so in sophisticated clinical trials, managed by compassionately guided professionals who care more about delivering patient benefits rather than money. I cannot guarantee we will be able to do all that has been envisioned, but I know we all work constantly to make this happened. And as I often say to those that will actually listen, "The only real failure is not to try."
Sincerely,
Alex Moffett, CEO