Stem Cell transplantation
Dr. Eva Feldman devoted 12 years to working on a drug-based cure for amyotrophic lateral sclerosis (ALS). It was, she says, “a very big endeavour.” It failed.…
Dr. Eva Feldman devoted 12 years to working on a drug-based cure for amyotrophic lateral sclerosis (ALS). It was, she says, “a very big endeavour.” It failed.
So, in 2006 the University of Michigan clinician/researcher took a sabbatical to rethink her approach to fighting ALS, the cruel, fatal condition that attacks the nerve cells (neurons) that control muscle movement. “I wanted a break,” she says. In California, Dr. Feldman found scientists doing interesting animal studies on treating spinal cord injury with stem cells. It changed her perspective entirely.
Today, with two early-stage human studies behind her, Dr. Feldman hopes to soon begin a large-scale clinical trial to test whether human neural stem cells injected into the spinal columns of ALS patients can stop the disease from stealing their ability to walk, talk, eat and breathe.
“We inject the cells into the high part of the spinal cord of patients with ALS with the goal of protecting the large motor neurons that are necessary to maintain normal breathing. Our goal is for the stem cells to go into that area, surround the neurons that are starting to get ill and nurse them back to health. We do very similar injections in the lumbar area of the spine to preserve the neurons that go to the muscles that allow patients to walk.”
Preclinical studies she and her team conducted on rats and pigs showed that the stem cells “take a really bad environment and clean it up.” Inflammation is ameliorated and the stem cells surround the large, ailing motor neurons and nurse them back to health. “The cells go from looking like they are about to die to being quite healthy and robust,” says Dr. Feldman.
Phase I and II clinical trials involving 30 patients went “extremely well,” she says, with the procedure proven to be safe and the patients able to tolerate the accompanying immuno-suppressant therapy. “We have good preliminary data,” she says.
Neuralstem Inc., Dr. Feldman’s industry partner in the project, is organizing a large, multi-centre trial in 2016 to test whether the procedure truly works. Richard Garr, the company’s Chief Executive Office, is understandably guarded about the details, saying via email that his company is working with the U.S. Food and Drug Administration and that “all of the issues with respect to the scope and nature of the trial are still being determined.”
Dr. Feldman, who has been down this road before with the failed ALS drug, is cautiously optimistic. “As enthusiastic as I am about the therapy, until we do a very large trial we simply won’t know with certainty that this is the hopeful home run that we want it to be.”
For Ted Harada, a 43-year-old former FedEx manager in Atlanta, Dr. Feldman’s stem cell therapy has been a life-saver. The recipient of two stem cell implant surgeries, he has seen his decline from ALS virtually stopped. The normal survival period for ALS, which is sometimes called Lou Gehrig’s disease after the New York Yankee slugger who succumbed to it, is about 36 months. He is now five years out and feeling good, although he still has the disease.
“I put my cane down two or three weeks after the (second) surgery and I haven’t picked it back up,” he says. “When I had my fifth year anniversary, my doctor said ‘Ted, I would have guaranteed you’d be dead within two or three years when I first met you.’ I like to say that the surgeries set the clock back to what I call onset.”
Dr. Feldman says other patients in the studies also have done well but “the numbers are small … until our numbers are larger we can’t say with certainty.”
While criteria haven’t been set, participants in the larger trial likely will need to be in the early stages of the disease, with the ability to breathe reasonably well and speak and swallow without difficulty. Dr. Feldman says Canadian patients might be eligible if they can travel to a surgical site — but, again, details are still being worked out.
Dr. Feldman is also excited about the possibility of using the same kinds of stem cells to treat the dementia disease.
“I have beautiful preclinical data in animal models of Alzheimer’s. We’ve shown that the injection of stem cells into the selected areas of the brain that are required to form new memories rescues the animals and they are able to function normally. We see the accumulation of amyloid, which is the build-up of plaque that patients get, gone. The stem cells go in and they are just like garbage disposals, cleaning up all the garbage. It’s remarkable.”
Canadian Blood Services (CBS) has officially launched the national public cord-blood bank.
“This is a significant achievement for the Canadian health care system,” Dr.…
Canadian Blood Services (CBS) has officially launched the national public cord-blood bank.
“This is a significant achievement for the Canadian health care system,” Dr. Graham Sher, CBS Chief Executive Officer, said in a press release. “Through our hospital partners, we are able to provide expectant mothers the opportunity to donate to a national public cord blood bank; increasing the chances for patients who need a stem cell transplant to find a match.”
As we reported in several articles here, the cord blood stored in the bank will be available to patients across the country who are unable to find donors among their families or donor lists. Cord blood cells are a rich source of stem cells, which can be transplanted to treat several diseases, such as leukemia and lymphoma. With only about 25% of patients able to find a suitable donor among family members, most patients need help from an unrelated donor.
CBS now has five collection sites in four cities: Vancouver, Edmonton, Ottawa and Brampton, Ont. Two facilities, one in Edmonton and the other in Ottawa, will test, process and freeze individual units of cord blood, while collections in Vancouver and Brampton will help increase the possibility of patients from different ethnic backgrounds — including Asians, Aboriginal People and multi-ethnic people — finding a match.
“Some of the mixed racial groups are the hardest to find a match for,” Dr. Jan Christilaw, President of BC Women’s Hospital, told the CTV News. “So the more diverse the bank is, the better the chance that if you really need cord blood stem cells for any particular reason, you’ll be able to find it.”
CBS has raised $12.5 million of the $48-million cost of the program for the next eight years, with contributions also coming from provincial and territorial governments (Quebec excluded as it has its own public cord blood bank).
Some time ago we blogged about the research into leukemia stem cells done by a team at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal.…
Some time ago we blogged about the research into leukemia stem cells done by a team at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal. This week, IRIC announced it is moving forward.
In collaboration with the Centre for Commercialization of Regenerative Medicine (CCRM), IRIC Commercialization of Research (IRICoR), has launched ExCellThera, a spin-off company that will improve the process of cord blood stem cell transplantation for patients with acute myeloid leukemia (AML). Click here to discover how stem cells are being used to treat leukemia and other blood disorders on our Toward Treatments page.
“We are excited to be working with CCRM to launch this new IRICoR spin-off company located in Montréal, which includes novel stem cell-expanding molecules that were initially identified and funded at IRIC via an early-stage investment from IRICoR,” Michel Bouvier, CEO of IRICoR, said in the IRIC press release.
ExCellThera is based on novel proprietary intellectual property related to the expansion of stem cells developed by two members of our Foundation’s Science Leadership Council: Dr. Guy Sauvageau, Scientific Director & CEO of IRIC, and Dr. Peter Zandstra, Professor at Institute of Biomaterials and Biomedical Engineering, University of Toronto and Chief Scientific Officer of CCRM.
A Phase I and II clinical trial, designed to test the ability of ExCellThera’s stem cell expansion approach, will begin this year at the Maisonneuve-Rosement Hospital in Montreal, and will grow to include Sainte-Justine Hospital and other centres in the near future. The trial will involve up to 25 patients suffering from AML.
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.”