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This was the week of RRY Publications' 4th Annual Stem Cell Summit, organized by investor and analyst Robin Young. Once again, Monya Baker, of Nature's stem cell blog "The Niche" does an outstanding job of summarizing the conference content and tenor in a post called "Investors ♥ stem cells". My only humble comment is that it might have been more aptly named "Entrepeneurs ♥ stem cells" because I don't think the plethora of companies and technologies represented at the conference was due to a flood of investment but rather the irrational (thank God!) enthusiasm of biotech entrepreneurs that keep sectors like this afloat whilst risk-averse investors await the obvious to float to the surface.
You owe it to your cells to find out what they know.
The big pile to hit the fan this week was the PLoS Medicine article published online February 17 describing a patient who developed “brain tumors” (glioneuronal neoplasms) after undergoing repeated transplants of “fetal neural stem cells” in Russia starting in 2001. Fellow bloggers Monya Baker @ the Niche (click here >>) and Alexey at Hematopoiesis.info (click here>>) both provide useful summaries and commentary .
Naturally it is a concerning report for the industry and the regulators. People jumped all over it touting their various perspectives and generating a veritable miasma of opinion. Indeed, so much so that Stem Cells, Inc (NASDAQ: STEM) was forced to publish a commentary on the report in an attempt to distinguish their product from what was apparently injected into the boy in Russia. STEM's commentary is worth the read.
What I will say here - apropos to my ongoing discussion about stem cell transplant clinics around the world enticing people to pay for a shot of stem cells because 'why not? these products are safe' - is that there are stem cells and then there are stem cells and then there are stem cell products. Products are well studied, well understood, well defined, well characterized, well controled, and well tested.
Ex-FDA, regulatory consultant Dr. Darin Weber (blogging at RegenmedGuru.com) has a great post on this whole issue that is well worth the read. He sums up his commentary by saying:
So why is the FDA "holding back" stem cell treatments that are available in other countries? Why should people think very carefully about their decision to go to a clinic offering stem cell injections for sale? Why is 'industry' critical of what some of these clinics are doing? Why should we be concerned about whether these 'treatments' are as safe as advertised? We now have an example of why.
The bottom line is that if you wish to test stem cells in humans in the U.S., the FDA is going to require robust evidence of efficacy and safety in relevant preclinical animal models, regardless of the source.Now the FDA has an clear example it can point to, for better or for worse, to justify the extensive preclinical studies it requires. The good news is that many developers of stem cell derived therapies, including Geron, have in fact been able to generate the preclinical efficacy and safety data needed to enter human clinical studies.
This is no justification for being over-reactionary about the potential for cell therapy. This is not even a good reason to paint all unregulated stem cell treatments with the same brush. It is a reason to be ever-vigilant in ensuring we are doing our utmost to produce effective AND safe therapies. It is also reason support the dialogue ISSCR is attempting to stimulate to help people discriminate between those clinics following best practices and those which are not.
In the meantime, people are getting shot up with sheep stem cells in Mexico (check it out) ...
No news is not really good news here.
Neuralstem, Inc. (AMEX: CUR) announced today its spinal cord stem cell trial to treat ALS has been put on clinical hold. This seems to be pretty par for the course at this stage. The question will be how long it takes to address the issues. Geron was able to get through their hold in under 9 months; ReNeuron submitted its IND to FDA in December 2006 and has yet to get it through despite being approved to proceed in the UK last month. See Monya Baker's commentary on Neuralstem's hold on Nature's stem cell blog, the Niche - click here >>.
Neuralstem was more forthcoming with details about their hold than Geron was when in the same position months ago. The FDA has reportedly provided the Company with specific comments, questions and recommendations for modifications to its protocol including requests for additional information regarding their product manufacturing process and pre-clinical studies, as well as their clinical delivery injection device and technique. The Company believes that it can "provide this information in an expeditious manner."
Apparently the Agency has also requested various modifications to the protocol and eligibility criteria for patients in the trial, as well as slight changes to the timing of the surgeries. Perhaps more interesting was the comments by President & CEO, Richard Garr that the "Agency had extensive 'non hold' comments, requests for information, and recommendations" which he characterized as issues which will need to be "addressed for final product manufacturing and testing". By that, I'm assuming he means the FDA raised several issues which wouldn't hold up phase I testing but certainly would need to be addressed in future stages.
As an extracorporeal cell-based bioartificial liver system, HepaMate™ is designed to combine blood detoxification with liver cell therapy to provide whole liver function in patients with the most severe forms of liver failure. HepaMate™ is comprised of a blood plasma separation cartridge, a hollow-fiber bioreactor filled with proprietary porcine liver cells, a charcoal column, an oxygenator, circuit tubing and a plasma reservoir. These components are assembled into a patented blood/plasma circulation system, which is placed on the HepaDrive™ perfusion platform.
A patented liver cell cryopreservation process provides for safe and easy storing and distribution of the liver cells which detoxify existing toxins, produce albumin and other liver-specific proteins when, during therapy, the patient’s plasma is separated from whole blood, exposed to the HepaMate™ bioartificial liver and returned to the patient.
The company claims only 90 minutes are required to assemble the system, prime the blood and plasma circuits and to process the liver cells due to the logistical advantages of its proprietary cryopreserved pig hepatocyte technology over the use of fresh cells from cell lines or liver tissue.
Thawing, loading and washing of the cryopreserved cells is reported performed at the patient’s bedside using a what the company describes as a proprietary, "FDA-approved" technique.
Apparently a retrospective statistical analysis of the previous pivotal Phase II/III clinical trial data, adjusted for the impact of liver transplantation on patient survival, revealed a statistically significant survival advantage for patients with fulminant and subfulminant hepatic failure when treated with HepaMate™ compared to controls receiving standard medical care alone. The company blames the previous trial's failure on the inclusion of a subset of 24 patients who had undergone a prior, failed liver transplant. It was these patients, the company postulates, that led the the phase II/III trial failing to achieve its primary 30-day survival endpoint in the overall study population. Based on the retrospective statistical analysis of the clinical trial data, HepaLife expects a new Phase III clinical trial without the inclusion of failed liver transplant patients to be successful.
The report indicated that the world's largest experiment using gene therapy to combat the AIDS virus yielded "a major advance," in demonstrating that the technique is valid, beneficial and safe. "It shows the potential of the gene therapy approach for the treatment of HIV and represents a major advance in the field... [it] can be developed as a conventional therapeutic product," the report stated. Yet later the report admited that while the treatment is safe efficacy was modest. Finally, the report states that in an interview, the principal investigator, Mitsuyasu, said they would not be proceeding past this Phase II trial to the final, third phase of the process. Instead, the team would learn from its experience, modify the technique and start again with tests on a smaller group of volunteers.
The paper was published in the February issue of the Bentham Open Stem Cell Journal. It outlines the long term results of the treatment of a patient for the treatment of Parkinson’s disease using autologous neural stem cells. According to lead author and NeuroGeneraton owner/founder, Michel F. Levesque, MD, FRCS(C), FACS, "We have documented the first successful adult neural stem cell transplantation to reverse the effects of Parkinson’s disease and demonstrated the long term safety and therapeutic effects of this approach."
The paper described a process by which tissue is taken from the patient's cerebral cortex and expanded for 6 months (yes, 6 month!) before injection. The paper's conclusions:
- Neural stem cells can be isolated from the human adult cerebral cortex, expanded in vitro using epigenetic factors, induced to differentiate into dopaminergic, GABAergic and other types of mature neurons, and selectively delivered back to striatal targets without immunosuppressant.
- Because of their biocompatibility, safety and potential integration into the host striatum, autologous neural stem cell-derived differentiatedneurons represent an alternative to current cell therapy aimed at the restoration of the nigro-striatal circuitry inParkinson’s disease.
MaxCyte, Inc announced the introduction of its GT Flow Transfection System at the 4th Annual Stem Cell Summit held in New York, NY this week. The MaxCyte GT Flow Transfection System is marketed as a a validated, scalable technology for customizing the biological activity of cells for therapeutic use. The system, the subject of a US FDA Master File, is designed to enable rapid and efficient transfection of primary cell or cell line with reported >90% cell viability following loading with a broad range of molecules (proteins, drugs, plasmids, mRNA, miRNA, and siRNA) or combinations thereof, at volumes up to tens of billion cells.
What's not clear to me is how this system is different from the clinical scale, non-viral cell loading systems MaxCyte has been selling now for some time and a quick spin through their website has not helped shed any light on that question. Indeed there is nothing about a product launch on their website so this product "introduction" might just be clever spin around a talk about a product that has been on the market for some time. I'll try to find out...
RESOURCES & EVENTS
Well, that's a wrap to an a wee bit of an odd but not entirely bad week in the cell therapy industry. For those of you with any doubts, remember you heard it here first: cell therapy means business.