Perspective

07
Apr 2014
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Jeff Biernaskie Screen Captuer

Jeff Biernaskie

The bald truth

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The Daily Mail, one of the feistier UK tabloid papers, recently blasted this headline across its health pages:

Have scientists discovered a cure for BALDNESS? 

The Daily Mail, one of the feistier UK tabloid papers, recently blasted this headline across its health pages:

Have scientists discovered a cure for BALDNESS? 

Would that it were true.  According to the Huffington Post, 80 million Americans “suffer from hair loss.” For Canada, then, about 8 million people are hiding hairless heads under their hockey toques. (Full disclosure: I am one of them.)

The article is based on research conducted at the Perelman School of Medicine at the University of Pennsylvania and published in Nature.  In a nutshell, Dr. Xiaowei “George” Xu, converted human skin cells into induced pluripotent stem cells to produce large quantities of epithelial stem cells, which are normally found in hair follicles. When transferred to mice, the cells created “recognizable” shafts of hair.

How recognizable is debatable.  But still, this represents an advance.

However, Dr. Xu urged caution: “We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet.”

Dr. Jeff Biernaskie (pictured at right) of the University of Calgary agrees. Any cure for baldness, he says, would have to incorporate re-invigorating dermal cell function.

“The problem is the dysfunction of these inductive dermal cells. Essentially, they either start providing wrong signals or they die off or atrophy. So the therapy that needs to be championed is actually restoring the function of dermal papillae cells. You need to revitalize those cells to restore hair growth.”

Dr. Biernaskie is not focused on finding new ways for follicles to grow on the heads of bald people. His lab is trying to decode how stem cells work to rebuild skin tissue for burn survivors, or people with chronic non-healing ulcers.

The reality, however, is that any stem cell researcher who could come up with a cure for hair loss would have the cosmetics industry pounding down their door. There would be billions of dollars to be made from such discovery — enough to set a researcher up for life, allowing him or her focus on tackling problems that can’t be solved with a wig or expensive hair transplants. “To be honest, I don’t know what could happen,” says Dr. Biernaskie, “but probably you would be financially set.”

Meanwhile, he and researchers around the world are trying to figure out the dermis puzzle.

“The reason we are working on dermis is that, while it’s a key target for restoring hair growth for conditions like androgenetic alopecia (male pattern baldness), it’s also critical for maintaining proper epidermal cell function and overall skin health. So if you can understand how to regenerate the epidermis and the dermis without forming scars and potentially generating new appendages (like follicles and glands) within that skin, that’s sort of a Holy Grail.”

Until then, the search continues. As does being bald.

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04
Apr 2014
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Obokata Capture 2

After the fury, will STAP stem cells stand up?

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The news this week that a Japanese researcher who claimed to have discovered a much simpler way to create stem cells has been found guilty of misconduct has sent a shock wave through the international stem cell community.…

The news this week that a Japanese researcher who claimed to have discovered a much simpler way to create stem cells has been found guilty of misconduct has sent a shock wave through the international stem cell community.

More importantly, it has everyone wondering:  does this revolutionary new method of making stem cells work?

In January, NewsDesk reported on the excitement generated by reports that researchers at the RIKEN Center for Developmental Biology in Kobe, working with a team in the Boston, had transformed blood cells from newborn mice into pluripotent cells called STAP cells.

The STAP (stimulus-triggered activation of pluripotency) process stresses the cells by exposing them to trauma, low oxygen levels or mildly acidic solutions so that they revert to an embryonic-stem-cell-like state. Lead author Dr. Haruko Obokata (pictured at right) of the RIKEN Center said work was already underway to replicate the technique with human cells.

Until now there have only been two basic ways of making stem cells: harvesting them from embryos (embryonic stem cells), or genetically reprogramming adult cells to function like embryonic stem cells (induced pluripotent stem cells). To put the impact of Dr. Obokata’s discovery in context, the 2006 discovery of induced pluripotent cells earned her countryman  Dr. Shinya Yamanaka the Nobel Prize in Physiology or Medicine in 2012.

However, on Tuesday, a RIKEN-led committee investigating six problems with the STAP findings, which were published in the high-prestige journal Nature, ruled that in two instances Dr. Obokata had intentionally manipulated data. Both dealt with images of the cells used to support the findings.

CTV carried an Associated Press report in which RIKEN Institute President Dr.  Ryoji Noyori said that, after allowing for an appeal, “disciplinary action would be taken, including calling for retraction of the suspect paper.”  Nature, meanwhile is conducting its own investigation.

For her part, Dr. Obokata has vigorously denied doing anything wrong and is appealing the decision, calling it “a misunderstanding.”

The fracas follows concerns over the use of several duplicated images in the findings as well as reports that scientists working in other labs have been unable to reproduce the same results by using the STAP process. The latter is not entirely surprising: it can take time to get a new process exactly right — especially one that is a revolutionary as what Dr. Obokata’s team came up with.

In fact, the RIKEN investigators haven’t said if STAP is scientifically valid.  Nature News reported that the committee “repeatedly fended off questions about whether the technology works and, thus, whether STAP cells actually exist,” quoting one investigator as saying, “That is beyond the scope of our investigation.”

 

Dr. Janet Rossant, Chief of Research and Senior Scientist at The Hospital for Sick Children in Toronto urges caution before passing judgment.

“The team in RIKEN is still continuing to believe in the basic finding and will surely be working to revalidate the findings,” Dr. Rossant wrote to NewsDesk in an email. “We await new reports from the lab in Japan and, critically, reports from other labs worldwide as to whether this finding can be readily and robustly replicated.”

So, while the storm around the misrepresented data rages, the scientific world waits to see if STAP stands up to the test of time.

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25
Mar 2014
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Tiny hearts = big deal for drug testing

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When the subject of using stem cells to treat disease comes up, most of us have an image of doctors injecting or infusing these building-block cells into a patient to stimulate the repair of their traumatized tissue or dysfunctional organs.…

When the subject of using stem cells to treat disease comes up, most of us have an image of doctors injecting or infusing these building-block cells into a patient to stimulate the repair of their traumatized tissue or dysfunctional organs.

We’ve written about this approach several times in this space — most recently reporting on a clinical trial to test stem cells in spinal cord injury.  We also reported on a 100-participant study led by Dr. Duncan Stewart at the Ottawa Health Research Institute infusing genetically enhanced blood stem cells into damaged hearts to generate healthy tissue, minimize scarring and prevent heart failure.

Those kinds of studies are called in vivo, meaning “within the living.” But researchers are also opening up entirely different front in the war on disease: using stem cells to create “models” of diseased tissue or organs for testing drugs. Called in vitro (literally, “within the glass” to signify experiments carried out in a Petri dish or test tube), these studies essentially set up a disease straw man for a potential therapy to knock down.

There are advantages to this approach: it skips the pre-clinical animal testing stage that can be a labour-intensive, time-consuming exercise. Imagine the frustration of spending months testing a new drug on rats only to find it’s a no-go. Also, what can show great promise in testing with genetically engineered, immuno-suppressed rats often doesn’t translate into something that will work on real, live, normal human beings.

One of the more promising examples of this kind of work is underway at the University of Toronto’s Institute of Biomaterials & Biomedical Engineering and the McEwen Centre for Regenerative Medicine. Researchers there have developed the first-ever method for creating living, three-dimensional human heart tissue that behaves just like the one pumping blood through your body as you read this. Their findings were published in the Proceedings of the National Academy of Science recently and, so far, have been picked up by 10 media outlets.

“It means basically having hundreds of small versions or models of hearts in one dish, which we can test drugs on to determine which one actually has positive effects,” explains Nimalan Thavandiran, a PhD student in the labs of Drs. Peter Zandstra and Milica Radisic, and lead author of the study.

The ultimate goal, he says, is to create a heart micro tissue that is healthy and then “artificially apply an insult to it” to make it more like a diseased heart. These damaged micro hearts can then be treated with drugs — some that are already on the market for treating other conditions — to see which ones are helpful.

The micro heart tissue can also do service to test the cardio-toxicity of drugs used to treat other conditions. “Often times, a drug to treat cancer will make it to the later phases of a clinical trial and then fail because of side effects on either liver or the heart. So this is why it is important to have human cell-based models, like cardiac or liver models to see early on if these drugs have any adverse effects. And if they do, you can do two things: you can either scrap the drug or you can actually figure out how to molecularly modify it to prevent the toxic effect.”

In the extremely expensive world of drug testing, where it can take hundreds of millions of dollars and many years to test a new drug, having a stem cell-derived micro tissue model represents a huge saving in time, money and resources that could be better spent elsewhere. That’s why many labs across the globe are working to create these models.

With the publication of their paper, Nimalan Thavandiran and his colleagues have shown how to significantly improve the formula for creating stem cell-derived cardiac tissue that behaves like more mature heart tissue. They have come closer than anyone to getting the mix right, factoring in the electrical and mechanical stimulation a heart experiences.

“The heart is consistently both being filled with blood and pumping blood, and so there is a constant mechanical force,” he says. “At the same time, the heart is constantly receiving electrical signals which help maintain synchronicity. All this is very difficult to recreate in a dish.”

They still have further to go, he says. “The ultimate goal is to be able to recreate a perfect micro environment for the heart so that we have an ideal model to screen drugs with.” But they are closing in on what could soon emerge as an important step in drug-testing.

“Until recently, researchers didn’t have the right micro fabrication techniques, the right materials, differentiation protocols, the right understanding of what co-factors are involved with these stem cell-derived heart cells. Now we have a relatively good understanding of all of these things.  It’s just the matter of putting it all together.”

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13
Feb 2014
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Our gold medal stem cell scientists

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While Canada’s athletes continue to pile up medals at the Winter Olympics in Sochi and prove their prowess on ice and snow, our stem cell scientists are demonstrating that they too are the best in the world.…

While Canada’s athletes continue to pile up medals at the Winter Olympics in Sochi and prove their prowess on ice and snow, our stem cell scientists are demonstrating that they too are the best in the world.

On the same day that 1,000-metre speed skater Denny Morrison came off the bench (courtesy of team mate Gilmore Junio surrendering his spot) to win silver, Dr. John Dick’s team at the University Health Network in Toronto showed the world what the origins of leukemia look like, publishing their findings in the prestigious journal Nature. That news comes hard on the heels of fellow UHN researcher Dr. Gordon Keller’s discovery of a key regulator that controls the formation of blood-forming stem cells, published in the top-tier Cell.

Both papers represent advances in how we understand and may someday treat disease. Without wanting to sound over-the-top patriotic, both prove that, as a nation, we continue to do outstanding work in the field founded by two Canadians — Drs. James Till and Ernest McCulloch — more than 50 years ago.

Essentially, Dr. Dick has identified a “pre-leukemic stem cell” that appears to initiate acute myeloid leukemia (AML) and, because chemotherapy doesn’t eradicate it, allows the disease to come back. Readers of this blog will recall that Dr. Dick was the first in the world to identify cancer stem cells. He proved that just as stem cells produce millions of specialized cells to build and repair tissues and organs (while also renewing themselves), cancer stem cells drive the production of millions of tumour cells (while also replicating themselves).

“What we found is the first normal cell, the cell of origin, that actually sets off the of cascade events, which is going to ultimately lead to leukemia,” Dr. Dick explains in the UHN video above. “So, one of the direct implications and benefits of our findings is that we should be able to detect leukemia before it arises. And, by identifying patients like that earlier, we should be able to follow them and introduce therapy an earlier stage.”

It should be pointed out that this is very early-stage work. To have application in cancer prevention or care, scientists must find a drug that can target a mutation in the gene called DNMT3 that causes these pre-leukemic stem cells to develop. Such a drug would have to be rigorously tested, something that could take years. But it’s still a very important advance.

“What’s John’s given us is something to go after before the disease gets out of hand,” says Dr. Mick Bhatia, Director of the McMaster Cancer and Stem Cell Biology Research Institute. “That’s a huge gift. It’s like stories about the unicorn. He has identified it, now we have to figure out how to capture it. What we have to grapple with is: ‘Are these pre-leukemic cells targetable?’ ‘Can you diagnose them?’ and ‘Can you shut them down before they become leukemic?'”

In his discovery, Dr. Keller, Director of the McEwen Centre for Regenerative Medicine, identified a key regulator controlling the formation of blood-forming stem cells in the early embryo. He focused on retinoic acid, which is produced from vitamin A and is vital in growth. His team demonstrated that the retinoic acid signalling pathway is critical to making blood-forming stem cells. In experiments with mice, the researchers found that blocking the pathway blocked the formation of blood-making stem cells. Activating it pathway set off an upsurge of blood-forming stem cells.

“Our findings have identified a critical regulator for directing pluripotent stem cells to make blood-forming stem cells, bringing us one step closer to our goal of developing a new and unlimited source of these stem cells for transplantation for the treatment of different blood cell diseases,” says Dr. Keller in Medical News Today.

This discovery is also early-stage work, but also very important, says Dr. Bhatia.

“He is capturing a pathway that is critical for when the first blood stem cell is born and how it makes copies of itself — the self-renewal process. That is going to be instrumental in how we move forward clinically.”

While neither finding is a cure for cancer, both are important steps forward on the path to get there. To push the Olympics analogy a bit further, this is like winning a preliminary competition that allows you compete in the medal round.

Except this is not a game and in this medal round, the prize is much more precious than gold.

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30
Jan 2014
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janet rossant rock star video3

Surprise: A whole new way to make stem cells

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News this week that Japanese and American scientists have found a third way to make pluripotent stem cells — a process that’s far simpler, faster and cheaper — is being heralded by some as a game-changing development in regenerative medicine.…

News this week that Japanese and American scientists have found a third way to make pluripotent stem cells — a process that’s far simpler, faster and cheaper — is being heralded by some as a game-changing development in regenerative medicine. Others say it may just be “a lab curiosity.”

Until now, there have been two main ways to create stem cells that are pluripotent (capable of producing any cell the body needs):

• harvesting them from embryos (embryonic stem cells), or
• reprogramming adult cells to function like embryonic stem cells (induced pluripotent stem cells).

Making embryonic stem cells has not been without controversy. And because creating induced pluripotent stem cells initially involved genetically altering things, there were concerns they could potentially cause tumours. While that problem apparently has been solved, the procedure is still a complex and costly one.

Now there is a third way — although, so far, it has only been done in animals. Researchers at the RIKEN Center for Developmental Biology in Japan and Brigham and Women’s Hospital and Harvard Medical School in the United States transformed blood cells from newborn mice into pluripotent cells called STAP cells. The technique involves stressing the cells by exposing them to trauma, low oxygen levels or mildly acidic solutions. Within days, the cells revert to an embryonic-stem-cell-like state. (A Boston Globe graphic illustrates the process beautifully. See it here.)

“It’s very simple to do,” Dr. Charles Vacanti of Brigham and Women’s Hospital in Boston, told the Associated Press after the two papers were published online Wednesday in Nature. “I think you could do this actually in a college lab.” Dr. Haruko Obokata of the RIKEN Center, said researchers are already at work to see if the technique can be replicated with human cells.

So, what to make of these new stem cells?

Dr. Chris Mason, chair of regenerative medicine bioprocessing at University College London, told Reuters that the approach was “the most simple, lowest-cost and quickest method” to generate pluripotent cells from mature cells. “If it works in man, this could be the game-changer that ultimately makes a wide range of cell therapies available using the patient’s own cells as starting material – the age of personalized medicine would have finally arrived.”

Others are more guarded. “Until you show it works in humans, it’s hard to know what the application is going to be,” the University of California’s Dr. William Lowry told AP. “For now, the question of whether it’s a lab curiosity or a big medical benefit; that’s still up in the air.”

To make sense of STAP, NewsDesk asked Dr. Janet Rossant (pictured above), Chief of Research and Senior Scientist at The Hospital for Sick Children for her assessment of this remarkable development.

“I don’t think it’s a game-changer,” says Dr. Rossant, President of the International Society for Stem Cell Research and one of the world’s leading embryonic stem cells scientists.  “A game-changer means we’re all going to suddenly stop what we’re doing and do something else. It’s a surprising and intriguing observation, suggesting that somehow there is an intrinsic pluripotency program that is sitting there, waiting to be revealed if we stress the cells.”

She describes this as “one of those findings where you go, ‘Hmmm, that’s interesting.’ Of course, this is all mouse, so there is a need for further replication by other groups and further explanation of what the mechanism is. And, of course, extension to the human situation if this is going to have practical relevance. As it stands, I don’t see people are suddenly going to stop making induced pluripotent stem cells by the standard route. Because these cells, whatever they are, are not exactly identical to embryonic stem cells.”

The really important thing, according to Dr. Rossant, is that this discovery shows there “are multiple states of pluripotency out there” to be investigated. “We need to understand more about what we mean by the pluripotent state and whether it is a state that (cells) can fall back into.”

The true test of induced pluripotent stem cells, which were discovered in 2006 and earned Japan’s Dr. Shinya Yamanaka a Nobel Prize, was the fact other labs around the world could replicate the results.  That will now be the challenge for STAP cells.

“It was a very surprising, intriguing result. It’s come from a reputable laboratory — RIKEN is one of the top developmental biology groups in the world,” says Dr. Rossant, who is a member of the Canadian Stem Cell Foundation’s Science Leadership Council.

“The question will be, ‘Is this a truly robust way of generating pluripotent stem cells?’ And only time will tell.”

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27
Jan 2014
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Fehlings Screen Captre

Spinal cord study: ‘This is no flash in the pan’

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Recently we blogged about a media report on a first-of-its kind North American study to test using neural stem cells to treat spinal cord injury (See Hope not hype).

Recently we blogged about a media report on a first-of-its kind North American study to test using neural stem cells to treat spinal cord injury (See Hope not hype). The small, Phase 1 clinical trial, sponsored by StemCells, Inc.  of California, is underway in Calgary — where the first patient has received his transplant — and Toronto. NewsDesk subsequently asked Dr. Michael Fehlings, head of the spinal program at Toronto Western Hospital and the lead investigator for the trial at the University of Toronto, to share his thoughts on the experimental treatment. In this edited transcript of the conversation, he describes the excitement at seeing the trial take place here in Canada, addresses ethical concerns and stresses the importance of managing patients’ expectations.  

Q: Is this the first time that this kind of thing has been done in North America?

A: Not exactly. This is the first the first trial with adult neural stem cells in spinal cord injury in North America. But Geron, which is another California-based company, got approval to use stem cells derived from embryonic stem cells and they injected four patients with traumatic spinal cord injury in the last couple of years. Then the company stopped the trial for financial reasons.

There has been a trial with neural stem cells in patients with Amyotrophic Lateral Sclerosis (ALS). That is a different company and they have completed the Phase 1 trial. So there is some precedent in the ALS field.

StemCells, Inc. has ventured into early phase human clinical trials in pediatric neurodevelopmental conditions. They did a small Phase 1 study in children with neurodevelopmental condition called neuronal ceroid lipofuscinosis and a Phase 1 clinical trial in children with a demyelinating condition called Pelizaeus-Merzbacher disease.

But this is the first trial of its kind using adult neural stem cells. We have found very convincing evidence for regeneration of the injured spinal cord injury and, particularly, we found that the neural stem cells are effective in remyelinating residual neurons in the host spinal cord.

This trial represents an important breakthrough in Canada as well, because it is the first of its kind (here). It does reflect an acceptance by Health Canada and will provide impetus for accelerating research at the pre-clinical level. Because there are many questions that will emerge out of the clinical arena that cannot be answered in a clinic. These will be addressed in pre-clinical laboratories and we will hopefully continue to move forward into the clinical pathways.

Q: I was impressed how CTV handled the report. They didn’t create the impression that people were going to jump out their wheelchairs with this.

A: I think it is a fair statement. I think that what this type of trial does is calibrate the discussion. We have moved on from the types of dramatic reports we heard with the so called “medical tourism” — dramatic claims that raise hope but are not supported by evidence. Here, the level of rigour to get a trial like this approved by Health Canada is extremely high.  I think for us it is really important and it is very exciting for the stem cell community because it shows that Canada is on the map. I think it is very noteworthy that this American company has chosen Canada as their entry to the North American platform.

Q: As you said, it is reassuring to Canadians that the work is being done here, that they don’t have to go everywhere and pay big dollars for suspect treatments.

A: Exactly. We are treating our own citizens and patients are not being charged anything. This is not being done for profit and we are making no claims, nothing but the fact that this is an exciting experimental treatment. It’s exciting, it’s hopeful, but we also have to be realistic. Ultimately, we are trying to determine what the effects of these cells are. We don’t know if the cells will work. We hope they will show an effect.

Q: These are stem cells derived from fetal tissue. Any concern about that? *

A: Anything in the arena of stem cells can potentially generate ethical questions for individuals. Whether we deal with embryonic stem cells, stem cells from fetal tissue, induced pluripotent stem cells. My response would be that the discussion is undertaken with the individuals with spinal cord issues and with their families, so they are aware what the source of the tissue is and if they have ethical concerns, their concerns are respected. On the other hand, it needs to be respected that the people have the right to have choice.

In terms of the source, I view this as a kind of the first step. Ultimately my hope would be that we could use our patient’s own cells. I would say that while I respect that there might be a minority of individuals who might express concerns, the cells come from tissue that otherwise would have been discarded. And because they are adult cells, the risk for forming a cancer or teratoma is extremely remote.

Q: Are you concerned that you might be swamped by people with traumatic spinal cord injury who want to take part? 

A: We are getting a lot of emails and a lot of requests. Most of the individuals who contact us are not candidates. It is a challenge to manage that. We anticipated that. We are trying to manage people’s expectations. We have a long-term commitment to this. This is no short term flash in the pan. It is a long-term strategy and commitment. We want to do things right, in a very responsible manner. We are trying to help people with spinal cord injury and to do the right thing.

* Editor’s Note: Stem cell research in Canada is conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, the Canadian Institutes of Health Research Updated Guidelines for Human Pluripotent Stem Cell Research and the Assisted Human Reproduction Act. For a more detailed explanation, click here.

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14
Jan 2014
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CTV Fehlings Capture

Dr. Michael Fehlings of Toronto Western Hospital

Hope not hype for spinal cord injury

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CTV News is to be commended for its excellent, even-handed reporting late last week of an exciting but early-

stage clinical trial to test using stem cell injections to treat spinal cord injury.…

CTV News is to be commended for its excellent, even-handed reporting late last week of an exciting but early-

stage clinical trial to test using stem cell injections to treat spinal cord injury.

The Friday report, originating in Calgary where the first North American patient has received the treatment, goes to great lengths to temper hope with the hard reality that a cure for spinal cord injury is many years away.

Reporter Karen Owen cautions that  “everyone’s expectations have to be realistic” and features University of Calgary neurosurgeon Dr. John Hurlbert talking about potential small improvements in patients’ quality of life, such as being able to hold a fork or button a shirt.

In other words, no one is raising false hope by suggesting patients might be rising from their wheel chairs and running down hospital halls any time soon.

The CTV website’s also offers an extended interview with Dr. Michael Fehlings, head of the spinal program at Toronto Western Hospital and the lead investigator for the trial at the University of Toronto, who articulately explains why it’s important for the public to hear about this kind of study — even though it’s so early in the game.

“It represents an advance in regenerative medicine technologies from the laboratory into the clinical realm,” Dr. Fehlings says. “This is  now a situation where the science has advanced to the stage where as rigorous a regulatory authority as Health Canada now feels the science is at a level where it can be ethically and scientifically studied in man. So this is a big deal in terms of the advance of the science.”

The North American trial builds on work already done in Europe where nine patients have undergone the treatment with no apparent adverse effects and some small gains observed. In essence, the researchers inject neural stem cells into the spine where there may be some intact nerve fibres to stimulate regrowth insulating layers called myelin. The goal is to restore electrical conduction along the spinal cord to restore muscle strength and sensation.

This is good news. It gives hope to the more than 85,000 Canadians who live with spinal cord injury. But it doesn’t set them up for disappointment by giving them hype.

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09
Dec 2013
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Colorectal cancer advance comes with a challenge

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When Dr. John Dick unveiled his latest cancer discovery last week, he also issued a challenge.

“I think this work will hopefully stimulate (drug) companies to get into the game,” he told the Toronto Star.…

When Dr. John Dick unveiled his latest cancer discovery last week, he also issued a challenge.

“I think this work will hopefully stimulate (drug) companies to get into the game,” he told the Toronto Star.

Dr. Dick, senior scientist at Princess Margaret Cancer Centre and the McEwen Centre for Regenerative Medicine, led a team of scientists and surgeons that found a way to disarm a gene called BMI-1 that regulates colorectal cancer stem cells.

In his own words: “When we blocked the BMI-1 pathway, the (cancer) stem cells were unable to self-renew, which resulted in long-term and irreversible impairment of tumour growth. In other words, the cancer was permanently shut down.”

Some context:  Dr. Dick was the first person in the world to identify cancer stem cells, the evil twin of the stem cell. Just as stem cells spark the creation of millions of specialized cells to repair and regenerate tissues and organs (while also renewing themselves) throughout a lifetime, cancer stem cells drive the production of millions of tumour cells (while also replicating themselves).

Current cancer therapies — essentially, surgery, chemotherapy and radiation — go after the tumour cells but leave the cancer stem cells unscathed. Which is why, researchers believe, cancer often comes back.

When Dr. Dick discovered the cancer stem cell — first in leukemia in 1994 and then in colon cancer in 2007 — he opened up a new front in the war on the dread disease.  With his latest finding, published in Nature Medicine,  he has provided a schematic diagram for building a major new weapon in that war. One that can be aimed at colorectal cancer, the third leading cause of cancer-related deaths in the Western world.

The discovery, which made news across Canada, is based on research conducted with mice. The team replicated human colon cancer in the rodents and identified BMI-1, a gene implicated in other cancers, as the pivotal regulator of the cancer stem cells, driving the cycle of self-renewal, proliferation and cell survival. Then they put an existing small-molecule inhibitor to work blocking BMI-1.

While the implications are enormous, there is a huge chasm to be bridged between working with mice and testing a drug  with people. It could take years and many millions of dollars.  But an important start has been made.

What happens now?

“So the next step … is to find the best possible drug to target this gene,” says Dr. Dick in a University Health Network video. “We’re actually testing a number of drugs that are able to target this gene. We’re trying to determine which is the best one and working with other investigators and other companies to try to develop and optimize the drugs so they can be delivered to patients in the best possible way.”

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02
Dec 2013
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Keep calm and carry on searching for cures

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A remarkable new Canadian report provides a snapshot of the state of “novel” stem cell clinical trials — those not about bone marrow transplantation for blood-based cancers — around the world.…

A remarkable new Canadian report provides a snapshot of the state of “novel” stem cell clinical trials — those not about bone marrow transplantation for blood-based cancers — around the world.

Published in Regenerative Medicine, The global landscape of stem cell clinical trials goes a long way to separate the hype from the hope around stem cell research and development.

The basic message of what the authors call “the most comprehensive account of the global stem cell clinical trial landscape to date” might be condensed to that recently refreshed British maxim from the Second World War: Keep calm and carry on.

“People have done it in a less systematic way,” says co-author Prof. Tania Bubela of other attempts to capture the global stem cell landscape.  “But they didn’t work out what’s new.”

Prof. Bubela, a lawyer and Associate Professor at University of Alberta School of Public Health, wrote the report with lead author Dr. Matthew D. Li of the Stanford University School of Medicine, and Dr. Harry Atkins, a clinician/researcher at the Ottawa Hospital Research Institute who specializes in stem cell transplantation for the treatment of autoimmune diseases.

They looked at every stem cell trial listed in worldwide registries up to Dec. 31, 2012. Of the 4,749 studies, almost 80% involve improving bone marrow transplantation using hematopoietic (blood-forming) stem cells to treat leukemia and other blood-based cancers — or treating transplant-related conditions.

That work has been going on for five decades, with more than 1 million transplants performed so far. It’s no surprise, then, that so many trials are being carried out in countries with established infrastructure for bone marrow transplantation. It shows that developing clinical capacity and technical infrastructure to process and deliver cell therapies will be crucial to the ongoing development of regenerative medicine.

Setting those trials aside leaves 22% — or 1,058 clinical trials — testing novel therapies for a variety of maladies ranging from kidney conditions (eight clinical trials) to cardiovascular disease (278). It’s on these non-traditional trials that the report focuses.

And the findings are enlightening:

  • In spite of enormous media attention, embryonic stem cells are being used in just a handful of clinical trials worldwide.
  • The use of allogeneic (donated) stem cells “has increased rapidly since 2009” but autologous procedures (using a patient’s own stem cells) still prevail.
  • Asian countries — especially China, but also South Korea, India and Japan — have surpassed the United States and Europe in volume of novel clinical trials.  Trials are also increasing in Australia, Brazil, Iran and Israel.
  • Industry partners are involved at least 25% the time, up significantly since 2004.  This is particularly true in American states such as California, where 50% of all trials involve industry sponsorship or collaboration.
  • Big pharma, however, is still on the fence: worldwide, most of the companies involved in novel trials are small to medium sized.
  • Despite gaps in knowledge about the duration of their survival and impact on surrounding tissues, mesenchymal stem cells (found in bone marrow, umbilical cord blood ,muscle and fat tissue) are being used Phase 2 trials for diabetes, pulmonary hypertension, chronic obstructive pulmonary disease because of their “regenerative and reparative” potential.

Prof. Bubela makes the point that not all clinical trials are created equal. Regarding the proliferation of trials in Asia, she cautions that “just because they are listed in a registry doesn’t mean they have proper oversight or regulatory approval.”  Some, she says, may be run by stem cell tourism operations — clinics that entice North Americans and Europeans to travel to their centres for unproven treatments that cost many thousands of dollars.

“You could speculate that they could be using it (the clinical trial) as a recruitment tool or for some form or legitimacy for the work they are doing.“

The report stresses that despite pressure from “patient groups desperate for therapies and cures for currently untreatable conditions” and “industry and policy makers eager to see a return on substantial investments,” moving treatments from clinical trials to clinical practice is going to take some time.

“If you look at the trajectory of any complex biologic (treatment), from R&D through regulatory processes, that just gives you market approval — it doesn’t give you a market,” says Prof. Bubela. “You still need to get clear reimbursement thresholds established.  To get the complicated stuff through, you can be looking at 20-30-year development pipelines.”

The report concludes that “the field is progressing at a steady pace, but the therapeutic rhetoric must be tempered to reflect current clinical and research realities.”

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Nov 2013
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A small clinical trial says big things about Japan

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Japan is moving forward with its plans to fast-track the use of induced pluripotent stem (iPS) cells to treat diseases — and revitalize its economy.…

Japan is moving forward with its plans to fast-track the use of induced pluripotent stem (iPS) cells to treat diseases — and revitalize its economy.

According to the Japan Times, the country last week officially passed a law “to promote safe and swift treatment using induced pluripotent stem (iPS) cells and other stem cells.” The legislation had previously received lower-house parliamentary approval.

As touched upon in an earlier post, Japanese scientists are now conducting world’s first human tests using iPS cells to treat age-related macular degeneration – the leading cause of vision loss in people over 50.

It’s no surprise they are first. Japan’s Dr. Shinya Yamanaka demonstrated how to create human iPs cells six years ago, inducing  adult skin cells to become pluripotent (capable of differentiating into any cell the body needs). These cells function much like human embryonic stem cells but come without any controversy over destroying embryos to create them. The downside to iPS cells is a safety concern that the reprogrammed cells could potentially cause tumours to form. Researchers in Canada and around the world have been working on solutions to that.

Dr. Yamanaka  won the 2012 Nobel Prize in Physiology or Medicine for his efforts. Throwing their support behind his work, Japan’s government recently announced it would invest more than $1 billion over the next 10 years in researching and developing iPS cells.

There is much more than national pride at stake, however.  According to Bloomberg News, Prime Minister Shinzo Abe sees cellular regeneration as a key element of economic regeneration. His government, the report says, “estimates that stem cells’ potential to rejuvenate worn-out body parts or reverse degenerative diseases such as Alzheimer’s may yield $380 billion in sales by 2050.”

The macular degeneration trial involves just six patients using iPS cells generated from their own skin. It is a  tiny study by any measure. But it represents a big step in the country’s efforts to develop a stake in that potential mega-billion-dollar market.

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