The Niche

Shortly after my coverage of the FDA’s approval for NeuralStem’s stem-cell trial for amyotrophic lateral sclerosis appeared on the Niche, Letizia Mazzini and Franca Fagioli of Eastern Piedmont University contacted me to tell me about their team’s work using mesenchymal stem cells for the same disease. While Neuralstem is moving forward with neural stem cells, Mazzini and colleagues have been exploring the use of mesenchymal stem cells derived from the patient who will receive them. She has recently published results of a Phase I trial as well as a review of stem-cell approaches in ALS. Unfortunately, I learned of this work only after I’d posted.

Continue reading "More stem cells in Lou Gehrig's disease" »

Posted by Monya Baker on September 29, 2009
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The Maryland company NeuralStem has the U.S. Food and Drug Administration’s permission to test its spinal cord stem cells in twelve patients with amyotrophic lateral sclerosis. The approval comes a month after the FDA placed Geron’s planned clinical trial on hold for a second time. NeuralStem’s trial had also previously been placed on hold by the FDA in February before receiving the go-ahead in September.

Though both trials involve placing cells into the spinal cord, NeuralStem’s product is made of cultured neural stem cells derived from a single 8-week fetus; Geron’s product, intended to treat spinal cord injury, is derived from embryonic stem cells that have been differentiated into precursors of neuron-support cells.

“This is certainly the first stem-cell approach for ALS,” says Lucie Bruijn, a scientist at the ALS Association, a patient group that also funds relevant research. Most other approaches for treating ALS are small molecule drugs, she says, and she’s not aware of other cell therapy or other invasive approaches entering human testing in the near future.

ALS has not funded NeuralStem’s work directly, Bruijn says, but has advised the company and funded academic scientists who’ve been involved with the company.

NeuralStem’s chief scientific officer Karl Johe says tests of large animal models show that the transplanted cells exert a neuroprotective effect over motor neurons, but it’s not entirely clear how. Earlier this year, Neuralstem and collaborators published results in a rat model of ALS showing that transplanted cells could develop into interneurons that formed synapses with the rats’ motor neurons.

However, Johe emphasized that the upcoming trial will assess safety rather than efficacy. The first few patients selected for the procedure will be those who are no longer able to walk. Because the injected cells protect rather than replace motor neurons, these sicker patients are less likely to benefit from treatment, but they are less able to lose function if something goes wrong. Cells will be injected only on one side of the spinal cord in order to minimize the number of injections into the spinal cord. Only one patient will be injected each month, so that researchers can monitor for effects over a longer period. Eventually, Johe says, the goal is to be able to inject cells in both lower and upper regions of the spinal cord in healthier patients, and see if the injections can keep motor neurons healthy.

The trial is expected to take place at Emory University in Atlanta, Georgia. Though the FDA is allowing the trial to go forward, the university’s patient-safety board will also need to approve the trial before it can proceed. Johe declined to say when that would be but said discussions were well underway.

Other companies using neural cells include ReNeuron, which received permission from UK authorities this January to start clinical trials for stroke. Its cell product is made from genetically modified cultures of neural stem cells, also of fetal origin.

StemCells Inc is conducting trials in Batten’s disease, a neurodegenerative disease that strikes children, and recently received approval for a clinical trial for a similar disease. It also uses neural stem cells from material originally derived from fetuses and has recently published results showing that its cell product delayed some symptoms of the disease by about three weeks.

As with human embryonic stem cells, the patent situation for neural stem cells is contentious. In a pair of dueling press releases this May, NeuralStem and Stem Cells Inc both claimed key intellectual property on these cells.

Posted by Monya Baker on September 21, 2009
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Yesterday, I reported on the failure of two late stage trials exploring mesenchymal stem cells to quell the potentally fatal immune response in graft versus host disease. Those trials were led by Osiris, a company in Maryland, which still hopes to look through its data and ongoing trials for signs of efficacy. See Stem-cell drug fails crucial trials

However, they are not the only researchers exploring mesenchymal stem cells: a search on clinicaltrials.gov pulls up 77 studies for a variety of indications. But some scientists are uneasy with the idea of using the cells to quell inflammation, because it’s not clear how they work.

A Karolinska University group published its findings of a 55-person trial in the Lancet, so I asked two of the scientists involved for their thoughts. I reached one, Katarin Le Blanc, in yesterday’s article. This morning another scientist, Olle Ringden, responded. “The findings here will probably preclude mesenchymal stem cells to be used as first-line therapy for acute GVHD.” Ringden, who is working to recruit patients for a similar, double-blind study in Europe, thought that one reason that the Osiris trial did not show efficacy is that the trial included only a few children, and children seem to respond better than adults. He echoedthe thoughts of LeBlanc’s and Pranela Rameshwarof New Jersey Medical School, a scientist uninvolved with either of the studies: “We need to find the optimal way of giving these cells and the optimal conditions. We probably need to find out why mesenchymal stem cells work in some patients and why it doesn't work in others.”

“The take-home message is that mesenchymal stem cells may be useful in steroid-refractory liver GVHD. In such patients, there was a significantly improved response and also durable complete response, compared to the placebo groups. Mesenchymal stem cells also improved the response rates in patients with steroid-refractory gastrointestinal GVHD. One reason for the poor outcome in this study in contrast to the European trial published in the Lancet may be that there were only few children included in this study (n=28). Children seem to have a better response rate compared to adults.”

Another company is exploring similar stem cells. The small company PluriStem announced this week that it would be starting a second Phase I trial of its product, described as a mesenchymal-like cell derived from placenta. A similar trial is reportedly also underway at Duke. Both trials are for critical limb ischemia, with the idea that these cells can help restore blood flow to jeopardized limbs. The company is also exploring other indications in which inflammation plays a role, including Crohn’s disease and multiple sclerosis.

Posted by Monya Baker on September 10, 2009
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Cross-posted from The Great Beyond

Last week, the US Food and Drug Administration put the brakes on Geron Corp's clinical trial in spinal cord injury because of just-completed animal studies that raised red flags. The Menlo, California-based biotech company announced Thursday that the animals developed microscopic cysts in the injury site. These lumps, however, did not spread to other parts of the body and none of the animals developed tumours. A second concluded study showed no cysts in spinal cord injured rats, according to a Geron press release.

“I think it provides people with a reasonable explanation,” said Stephen Brozak, an analyst with WBB Securities LLC in Westfield, New Jersey. “Everybody was afraid of the T- word, teratomas, and it clearly wasn’t that.” (Bloomberg)

Analysts rejoiced at the news. Geron shares rose more than 3% yesterday, closing higher than any day since the clinical hold was announced.

Geron is now working with the FDA to relaunch the stalled trials, the company said. No date was set.

by Elie Dolgin

Posted by Monya Baker on August 28, 2009
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Six months after giving it the green light, the U.S. Food and Drug Administration has told Geron to put plans for a clinical trial in spinal cord injury on hold. The company has differentiated embryonic stem cells into precursors of cells known as oligodendrocytes, which help keep neurons alive. Geron hopes this cell product could promote healing in people who have recently severed their spinal cords.

In a press release, Geron said that the hold was placed after the company submitted data on animal studies done to support delivery of increased doses of its cell product and on animal studies applying the cell product to other neurodegenerative diseases. (See the story from the San Jose Mercury News; here’s the Nature story when trial won approval)

I asked Evan Snyder, who directs the stem cell program at the Burnham Institute and is not privy to the confidential information, to speculate what might have been in the preclinical data that prompted teh FDA's action. It’s possible that the FDA just wanted more time to review newly submitted data, he said. Or on the other end of the extreme perhaps some sort of tumour or adverse reaction had been observed in the animals. Most likely, he thought, given that the company is trying to make larger doses of the cells, is that undifferentiated or non-neural cells have been observed in the cell product.

Clinical holds are not unusual particularly for innovative therapies. The FDA issued a clinical hold for NeuralStem in February on a trial in Lou Gehrig’s disease (the company uses neural stem cells derived from fetal cells)

At a large FDA advisory committee meeting in April last year, experts discussed the risks and benefits of products derived from embryonic stem cells. They were particularly concerned about uncontrolled cell growth. Even if the cells are not cancerous, tumours in the contained spaces of the brain and spinal cord could be devastating. Committee members were particularly concerned for diseases that are debilitating but not immediately deadly, since adverse events caused by experimental procedures could mean that people with years to live die early or end up suffering more. Patient advocates protested that they should be allowed to decide whether to take that risk.

See previous posts: Overview of FDA meeting (includes links to transcripts)
Nitty-gritty questions for making safe products
Posted by Monya Baker on August 18, 2009
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Two groups of researchers have at last completed a stringent test to show that induced pluripotent stem cells have the same developmental potential as embryonic stem cells: inserted into a special embryo, they can contribute to all the cells in a new mouse, litters of which have now been produced. (See the Nature news story)

GoogleNews was saturated this morning with stories of how to regenerate the heart:

Continue reading "Round-up of regenerative medicine stories and a big, squeaking accomplishment" »

Posted by Monya Baker on July 23, 2009
Categories: Clinical trials, Heart, Regenerative medicine, Reprogramming/Pluripotency | Permalink | Comments (0) | TrackBacks (0)

Regulatory authorities in India have, for the first time, given the green light for clinical trials to test stem-cell products, according to an article in Nature Biotechnology. Sponsored by Stempeutics, those trials will test mesenchymal stem cells in patients who with critical limb ischemia or who have had heart attacks. Like a handful of other trials, these cells will be derived from the bone marrow of healthy donors, processed or expanded in vitro, and injected into diseased patients. (See Questioning the Self Cell)

Meanwhile, an unrelated article in the Times of India suggests that, because the US will soon be able to fund more human embryonic stem cell research, India could soon become a hotbed of clinical trials for products derived from these cells. The article includes a quote from the head of a prominent Indian eye clinic stating that most work in India is in non-embryonic stem cells.

Like him, I don’t believe that the Indian market will be flooded with embryonic stem-cell trials anytime soon. Geron is supposed to start trials this summer in spinal cord injury; it needs only a tiny number of patients, with very specific kinds of injuries. Neither Novocell or the London Project will be ready to test their products for, respectively, diabetes or blindness, for several years.

I remember that, at the ISSCR meeting last year, Alok Srivastava, head of the Centre for Stem Cell Research at Christian Medical College, Vellore, described the procedures unregulated clinics in India were performing on paying patients. His argument was that if these clinics could be persuaded to characterize their cells and monitor their patients, the scientific community could glean valuable information. Still, he admitted, such open reporting would usually be at cross-purposes with those trying to make the most money most quickly. (For an analysis of the multiple conflicting motivations in unregulated stem-cell therapies, see our commentary from last year.

Srivastava is on the ISSCR committee that drafted guidelines for conducting clinical research on stem cell products. See Stick to the guidelines and fewer get hurt

Posted by Monya Baker on June 15, 2009
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Transplants of a fetal neural stem cell product seem safe, according to a 12-month study on six children with a horrible neurodegenerative disease called neuronal ceroid lipofuscinosis or Batten disease. Furthermore, the company reported results from an autopsy of a treated patient who died from the disease. (See Girl dies in stem cell trial for Batten disease ). These indicate that the injected cells engraft and survive in the brain for close to a year.

Continue reading "StemCells clinical trial results: Cells survive, seem safe" »

Posted by Monya Baker on June 08, 2009
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A patient death from unknown causes has led the company Aastrom to halt its clinical trial in which a mixed population of bone marrow cells is injected into patients’ heart muscle. The trial uses cells collected from the same patient who will receive the injection, and was examining the potential to treat heart failure caused by dilated cardiac myopathy.

Here is the press release from Aastrom. Here’s what's essentially a shortened version from Reuter’s.

There are a lot of trials using a patient’s own stem cells to treat heart disease; so far they don’t seem to do much benefit, but they don’t seem to cause harm either. See our 2008 feature, Stem cells for the heart, a new wave of clinical trials.

Aastrom’s is an unusual delivery method in injecting the cells right into the heart muscle, and it looked like it was gaining traction. See this report in the Times of India, which doesn’t mention Aastrom, but does refer to an affiliated scientist, Amit Patel. Patel gave the rosy update on Aastrom’s clinical trial on May 5th, a couple weeks before the death was announced. At that point, 13 of a desired total of 40 patients had been enrolled in the trial.

This year, there have been some positive results from Osiris and new approaches using sorted cells announced for using stem cells in heart failure.

Still, scientists have expressed strong doubts about whether bone-marrow derived cells will provide lasting benefits in heart failure. (See Q&A with Christine Mummery)

Posted by Monya Baker on May 22, 2009
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A transplant of blood stem cells in early onset diabetes seems to stop the immune system’s errant attacks on patients’ insulin-producing cells and so allow 20 of 23 patients to forego daily injections.
Read about the new JAMA study in Bloomberg. The work moves forward previous research on diabetic children carried out in Brazil.
The authors have previously reported using this system to stop errant immune attacks in an early study for multiple sclerosis. The strategy of the treatment is not to replace the tissue lost to the disease, but to stop the body from destroying itself.

Posted by Monya Baker on April 14, 2009
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In response to my last post, I wondered what Chris Scott's analysis of clinicaltrials.gov would say if he looked for fetal stem cells. He just told me he did the relevant search, and came up with nothing. In fact, one trial by StemCells that does use fetally derived cells does not say so in its clinical trial description. (See his post and several interesting comments at the link above.) Christopher Scott directs the program on stem cells and society at Stanford.

Scott has told me before that he is concerned that, because of enthusiasm for stem-cell research, clinicians may be including the term “stem cell” in clinical trials even if what’s being transplanted are poorly purified and characterized mixtures likely to contain stem cells. When I asked him about his recent analysis, he said he couldn't prove whether or not stem cells had been carefully purified or characterized. "It's just that the words "stem cell therapy" sounds sexier than "cell therapy" which is more accurate because most studies transplant populations of cells "enriched" for stem cells."

I suppose similar PR reasoning can explain the dearth of "fetal stem cells" in the database. A more charitable explanation would be that, of course, fetal stem cells is as poor a descriptor as is adult stem cells, since fetuses have already formed all their major organs. All the trials I know of using fetal cells use fetal neural cells. (But see my last post for more on that.)

Posted by Monya Baker on March 23, 2009
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The number of U.S. registered clinical trials using stem cells increased from 709 at in summer 2007 to 2,319 today. For trials using stem cells in heart disease grew by 110% last year (from 118 to 56); Parkinson’s disease fell by 100% last year (from 1 to 0). That’s according to an index of clinical trials just posted by Stanford’s Chris Scott.
Scott examined used the world’s largest registry of clinical trials to see how many included the term stem cells, categorized them, and then compared results between two years. Not surprisingly, the vast majority of trials were in hematology and oncology indications, for which bone marrow transplants, which contain stem cells, have been practiced for generations. One comment notes that as little as 5 years ago, all such trials would have fallen under that indication.
Scott offers caveats for his analysis. In particular, not every hit in a text search need be real. Nonetheless, the numbers are fascinating.
One category the analysis does not explore is trials using fetal stem cells. Those that I know of are all for neurological indications, and at least three have received or asked for regulatory approval to start trials within the twelve months. (The trials that have been given the green light are StemCells and ReNeuron.)
Given reports that a boy developed tumours in his brain and spinal cord after an unregulated (and highly criticized) stem cell procedure, this would be an interesting category to watch. In fact, just days after the reports came out, the FDA told NeuralStem to put its plans for a clinical trial on hold.

As research on all types of stem cells grows, it will be very interesting to see how the mixtures of cell types and indications studied shifts.

Posted by Monya Baker on March 22, 2009
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The FDA has ordered a halt to NeuralStem's plans for a neural stem cell trial in Lou Gehrig’s disease (amyotrophic lateral sclerosis). (See the company’s press release as well as a link to its December announcement that it had filed an IND) NeuralStem says that the FDA’s concerns and recommendations can be readily addressed.

Clinical holds are not unusual, especially for novel therapies. In fact, Geron received a clinical hold in May 2008 before ultimately getting permission to proceed in January 2009. In July, Geron plans to use cells derived from embryonic stem cells to treat spinal cord injury. (See the Nature story) I covered the hold in a blog posting, which also contains links to a summary of the FDA advisory meeting on how to evaluate safety risks for cells derived from embryonic stem cells. Hopes were high at that meeting. So was anxiety.

The FDA’s decision to delay NeuralStem’s trial comes just days after descriptions of an unregulated transplant of fetal neural stem cells that developed into tumours in a patient’s brain and spinal cord. The patient, who has a neurodegenerative disease, was taken by his parents for an unregulated stem cell therapy in Moscow. Doctors in Israel found the growths after the patient complained of headaches.
See the Nature News story. Researchers and physicians I spoke to while reporting the story were outraged that the procedure had occurred. They said that there was no evidence that it could help, and that no rigorous safety studies or even cell characterization had been completed. They took pains to distance the procedure from mainstream clinical research, but at the same time emphasized that all novel treatments carry risk.
(See our expert commentary on unregulated stem cell treatments, which has links to guidelines from the International Society for Stem Cell Research)

Stem-cell treatments involving bone marrow are well established, and though evidence of benefit for mesenchymal stem cells is still preliminary (See Nature Reports story), they do not seem to cause harm. Stem-cell treatments for neurodegenerative diseases are still very much at the beginning. Even with rigorous studies, the field will likely have more questions than clarity for some time to come.

Posted by Monya Baker on February 20, 2009
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The mesenchymal stem-cell company Osiris has announced positive results of its two-year 53-patient trial in heart disease. According to the press release,
patients receiving Osiris’s product Prochymmal had fewer arrhythmias. About 12% of treated patients had arrhythmias compared to 47% of those receiving a placebo treatment. (Even though the press release reports percents, remember that there are less than 100 patients in the trial). Osiris also reported no immune-related side effects. That’s significant, because unlike other adult stem cell therapies which return a patient’s own cells back into the patient, Osiris uses cells collected from the bone marrow of healthy donors. (But see a cautionary report from a mouse study)

A recent article in Nature Biotechnology (subscription required) describes the $1.38 billion dollar deal ($130 million upfront) that Genzyme made with Osiris for its mesenchymal stem cell technology. These cells are thought to secrete factors that help the heart heal itself.

Osiris is planning a 220-patient phase II trial for patients that have experienced a single heart attack. According to the company, “efficacy endpoints determined from cardiac MRI include end systolic volume, LVEF and the ability of Prochymal to preserve functional heart tissue, or limit scar formation following a heart attack. In addition, functional and quality of life assessments will be performed.”

This is one of several approaches to using stem cells in the heart. We covered these in a feature last year:
Stem cells for the heart, a new wave of clinical trials Also see a review by Andre Terzic on how stem cells can be used in regenerative medicine that just came out this month.

Just last week, researchers announced plans to launch a clinical trial testing another approach. That will biopsy heart tissue from heart attack patients, extract stem cells from it and reinject the stem cells into the scarred areas of the heart. This was written about in BusinessFirst of Louisville, Kentucky.

Q&A with Christine Mummery: Regenerating the heart

Posted by Monya Baker on February 13, 2009
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There’s a lot of reading material on the fact that Geron now has the FDA’s blessing to start a clinical trial for spinal cord injury using cells derived from embryonic stem cells. But some of the patients who have been waiting most eagerly for this announcement will be disappointed. The trial, which is expected to begin this summer, will only accept patients whose injuries occurred recently, within a week or two of the experimental treatment.

Coverage by Nature points out that other companies hoping to use embryonic stem cells for therapies are coaxing them into very different types of cells. It quotes Sean Tipton, former head of the Coalition for the Advancement of Medical Research "This is a trial of one particular application, not a trial of all embryonic stem cells."

The New York Times article explores the repercussions of what might happen if this trial disappoints or worse. (A topic Nature Reports covered more generally in Weighing risks and rewards on the way to the clinic.)

There is also an in-depth piece by Wise Young, the Rutgers neuroscientist who works tirelessly to investigate and explain emerging scientists to the spinal cord injury community. He puts the work leading up to the trial in context and then explains what it will mean for those already injured.

California Stem Cell Report’s David Jensen has a round-up of the coverage, with quotes from what he calls “not-so-ebullient views.” He also has posts on following Geron’s stocks, and a grateful note from a stem cell advocate.

In my first post announcing the trial, I included links to many of the questions raised as well as the context leading up to the trial.

Posted by Monya Baker on January 28, 2009
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The FDA has given permission for Geron to try an embryonic stem cell based therapy for spinal cord injury in up to 10 patients. The approval was granted on Wednesday, just a day after Barack Obama's inauguration as president, but both FDA and Geron say the timing is coincidental, according to an article in the Wall Street Journal.
Here is a press release from the company.

In spring last year, the FDA refused to let the trial go ahead. Analysts and advocates I spoke to were convinced this was because of political reasons, but that opinion was not shared by the half-dozen or so scientists I spoke with (some of whom credibly claimed inside knowledge of the proceedings). Though embryonic stem cells have potential to become any sort of cell in the body, regulators, scientists, and others worry that the cells are unpredictable. Since spinal cord injury is not a fatal disease, regulators fear that an experimental therapy that goes wrong could shorten someone's life. At the FDA hearing I attended in April last year, patient advocates pled with regulatory officials to consider quality and not just length of life when weighing the potential risks and benefits of a new treatment.

Here are some related articles:
Weiging risks and rewards on the way to the clinic
What stem cell therapy can learn from gene therapy
FDA places Geron's clinical-trial on hold (free blog from May 2008)
Embryonic stem-cell trial placed on hold (subscription news from May 2008)
FDA to vet embryonic stem cells' safety (subscription news, preview of the meeting)
FDA questions on making safe products from embryonic stem cells

Posted by Monya Baker on January 23, 2009
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ReNeuron has just received permission to launch a clinical trial for stroke patients using neural stem cells. About a dozen patients will receive the cells at Southern General Hospital in Glasgow, Scotland. An article in the Financial Times chronicles the path to obtain regulatory permission to launch the trial in the UK. An article in NatureNews describes how the cells, derived originally from aborted fetuses, have been genetically engineered with an inducible gene to control cells’ growth. The prospect of transplanting genetically engineered cells worried advisors to the FDA’s panel on starting clinical trials with embryonic stem cells last year, though Geron is still pressing ahead on this front.

Also, read about clinical trials underway with Osiris from a recent interview with the CEO Randall Mills.

For more information, see my December post on other non-embryonic stem cell trials that have launched recently.

Posted by Monya Baker on January 22, 2009
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Here’s a round-up of press releases and news articles of recent clinical trials in stem cells. Got something to add, email theniche[at]nature[dot]com

NerualStem has filed an IND to use its neural stem cell technology in a trial for Lou Gehrig’s disease.

StemCells, which already has a trial underway for Batten disease, just received FDA approval to start a trial for Pelizaeus-Merzbacher Disease (PMD), also a fatal brain disorder that affects mainly young children. The mechanism of the potential Batten disease therapy is to establish healthy neural cells that can help a patient’s own cells clear out some toxic garbage that builds up in the disease, the mechanism for PMD is to boost myelinization of neurons. (For work from a group that I think is unrelated, see Human cell transplants stop the shivers .) StemCells uses cells originally derived from fetal tissue.

Cytori has a 30-person clinical trial underway using fat stem cells for radiation induced injury.

Posted by Monya Baker on December 18, 2008
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Want to know about bone marrow transplant programs in Morocco or Pakistan or just about anywhere else in Africa, Asia or the Pacific? What about such programs for graft-vs-host disease, leukemia, anemia, or immunodeficiencies?

A special issue of Bone Marrow Transplantation has long summaries of all this and more, based on proceeding of a meeting last November

Posted by Monya Baker on August 18, 2008
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The ISSCR today condemned unproven stem-cell treatments that are not designed to learn and report information and that are conducted without oversight, particularly if patients are charged for advertised medical services. Originally a task force within the ISSCR was supposed to release a draft of guidelines on Thursday. After disagreements about how specific the guidelines should be and how stringent a tone to take, the group decided instead to announce over-arching principles at its annual meeting.
The ISSCR particularly condemns giving unproven treatments that are advertised as medical services for paying patients. In fact, instead of stem-cell treatment, the preferred term is “stem-cell based intervention” because the term “treatment” denotes benefit.
See Stem cell scientists face down stem cell tourism
The guidelines will be very broad, basically laying out how to decide when stem-cell product is ready to be tested in people. They will cover how cells should be processed and characterized, what pre-clinical evidence should be collected, how strong the case against risk and for benefit should be, how patients should be informed. They should also consider who research stands to benefit society as a whole.

Continue reading "Stem-cell society condemns undocumented human treatments without oversight" »

Posted by Monya Baker on June 12, 2008
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The first product derived from embryonic stem cells has been placed on clinical hold by the FDA, according to a company announcement today. Geron's product GRNOPC1 consists of oligodendroglial progenitor cells derived from embryonic stem cells and is being developed to treat acute spinal cord injury. The clinical hold means that Geron will not be able to start its trial, presumably until it addresses concerns raised by the FDA. In a statement, Geron said that it had received only verbal communication about the clinical hold and could not yet offer an explanation of the decision.

Geron was one of three companies invited to present to the FDA in April about what evidence needed to be presented about the safety of such products. The FDA's chief concerns were 1) characterization of cell product (are the mixtures of cells predictable and free from contamination?) 2) the possibility for unwanted growth and differentiation both from the desired cell type and contaminating cells 3) potential unpredictability of cells 4) difficulty in monitoring cells for harmful effects or retreiving cells for such reasons. Also, the FDA was concerned that the animal tests performed to evaluate cells could be much less predictive even than for animal tests for small molecule or protein drugs.

CIRM's scientific head, Marie Csete, has clearly explained the issues of putting cells into people in an interview.

I covered the FDA meeting in April with two blog posts:
Gearing for nitty gritty questions in clinical trials
plus an overview of the meeting.
A comment in the overview links to the slides and transcripts of the meeting.

Posted by Monya Baker on May 14, 2008
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On Thursday, April 10, the FDA held its first public advisory committee on assessing safety risks of cell therapies derived from embryonic stem cells. In a hotel ballroom just outside Washington, more than two dozen committee members and invited specialists weighed in. Separated from the discussion area by a yellow plastic chain, were about 200 prominent academics, consultants and industry representatives, and members of the press.

Prior to the meeting, the FDA had released a 12-page briefing document outlining the safety questions to explore, particularly how cells should be characterized and assessed for safety before transplantation and how patients could be monitored afterwards.

The biggest concern is that once placed in human subjects, cells could proliferate and differentiate in ways that are harmful and uncontrollable, and that studies of human cells in mice and rats won’t reliably predict their safety in human patients. A transcript of the session should be available from the FDA in a few months. Here’s about 2,000 words of what I found salient. (Disclosure: I was fresh off a red-eye from San Francisco, and I’m writing this on the plane back.)
Previously, I ran around asking attendees for their top-level thoughts. You can read that here. The consensus of the advisory committee for cellular, tissue, and gene therapies seemed to me to be both “Onward!” and “Careful!”

The sections that follow are 1) company presentations 2) wanted: fortune-tellers for teratomas 3) why can’t a mouse be more like a patient? 4) cell products are special and 5) once a trial enrollee, always a subject?

Continue reading "Gearing for nitty-gritty questions on making safe products from embryonic stem cells" »

Posted by Monya Baker on April 12, 2008
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