Adult Neural Stem Cells

13
Aug 2015
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Dr. Ivar Mendez

A stem cell solution to Parkinson’s?

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Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing.  …

Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing.  Walking becomes a stiff-limbed shuffle.

While drugs such as levodopa and dopamine agonists have greatly enhanced quality of life for Parkinson’s patients, their effectiveness diminishes over time. Deep brain stimulation has also proved helpful, but it does not slow the pace of neurodegeneration.

Stem cell transplants, however, may offer a longer-lasting solution.

“I think Parkinson’s is going to be the first neurological condition where stem cell therapy will be used widely,” says Dr. Ivar Mendez, Unified Head of the Department of Surgery at the University of Saskatchewan.  “We’re looking at transplanting one cell type. So we can direct the stem cells to become that type of cell — a Group A9 dopaminergic neuron.”

Transplanting cells into the brains of Parkinson’s patients in the hope of restoring dopamine neurotransmission is nothing new: it’s been going on for more than 25 years.  The results, according to a 2013 report in The Lancet, “have been variable and, thus, the merits of this approach have been both questioned and championed.”

The variation in results has been attributed to, among other things, the use of different strategies or protocols for transplanting the cells.  A key Canadian contribution to solving that problem is the Halifax Protocol for injecting cells into the human brain. Developed by Dr. Mendez, who was then at Dalhousie University, in collaboration with researchers from Toronto, Montreal and Calgary, the Halifax Protocol is regarded as the gold standard for effective brain repair using cell implantation.

“We developed the methodology for clinical transplantation,” says Dr. Mendez.  “When reviewers looked at all the grafts of all the patients who have been transplanted across the world, it was felt that ours did the best, in large part because of the methodology we developed.”

Dr. Mendez is working with fellow Parkinson’s stem cell pioneer Dr. Ole Isacson of Harvard to use induced pluripotent stem cells created from skin tissue to make dopamine-generating cells that, once transplanted, will integrate into the brain circuitry and restore motor function.

The process is autologous, meaning the stem cells come from the patient themselves, so no immunosuppression therapy is required. As well, researchers have come up with ways to generate the millions of cells required and have developed processes to make those cells robust enough to do the job.  So far, tests with large animals have shown positive results.

“We are continuing to work with animal models until we’re ready to start on a clinical trial, which should go ahead probably in the next two to three years,” says Dr. Mendez. “But I’m always concerned not to build unnecessary expectations among people affected by the disease.”

Other research centres are also working on a stem cell solution to Parkinson’s, with clinical trials using fetal cells currently underway in the United Kingdom.

“We’re very enthusiastic,” says Dr. Mendez. “Resolving the issue on a long-term basis, that is really the attraction. If one cell deteriorates or degenerates with time, can we actually replace that cell and reconstruct the circuitry? If we can, it’s a one-shot procedure. You do it only once and then the transplant will integrate into the host.”

Such a solution, however, could still be many years away.  Researchers need to be sure the cells they inject will do the intended job, without causing additional problems or perhaps generating tumours.

“We’re quite advanced in terms of realistically looking at a clinical trial,” says Dr. Mendez. “But we have to make sure that the preclinical scientific evidence is solid to ensure success”

[Find out more about stem cells and Parkinson’s here.] 

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03
Sep 2014
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P.K Subban took the Ice Buck Challenge

The Ice Bucket phenomenon and the excitement about stem cells

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P.K Subban has done it. So has Mike Holmes. And Toronto’s infamous Mayor Rob Ford.  Have you poured a bucket of ice water over your head to raise awareness — and funds — about ALS?…

P.K Subban has done it. So has Mike Holmes. And Toronto’s infamous Mayor Rob Ford.  Have you poured a bucket of ice water over your head to raise awareness — and funds — about ALS? (more…)

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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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