What will it take to move regenerative medicine forward so that it can deliver more cures and treatments for age-old diseases?…
What will it take to move regenerative medicine forward so that it can deliver more cures and treatments for age-old diseases?
That’s the subject of the First PanCanadian Strategic Forum on Cell and Gene Therapy to be held March 9 and 10 at the Westin Montreal.
“The cell and gene therapy ecosystem in Canada is coming to a level of maturity where we’re going to be ready to reap the fruit from it,” says Dr. Anne-Marie Alarco, former Chief Scientific Officer of CellCAN — Regenerative Medicine and Cell Therapy Network. “But it’s not going to happen passively. We have to put action in place.”
CellCAN is organizing the Forum in partnership with the Centre for Commercialization of Cancer Immunotherapy (C3i) and BioCanRx.
There is a sense of urgency to begin harvesting the “low hanging fruit,” says Dr. Alarco. Otherwise, she says, Canada could miss out.
Unlike the annual Till & McCulloch Meetings, which focus on the most recent scientific advances in cell therapies and regenerative medicine, the Strategic Forum will concentrate on what’s needed to move therapies into the clinic. Organizers expect to draw a range of academics, scientists, health agency representatives, government regulators, venture capitalists and business leaders from pharma and biotech.
“The idea is to bring together all the major stakeholders,” says Dr. Alarco, “to determine where we are in terms of cell therapies and gene therapies. We have all the elements for what we hope will be an interactive conversation. Hopefully, we will come up with a number action items.”
Lectures and workshops will consider ways to overcome barriers to implementing cell and gene therapies in Canada; build on effective commercialization for the benefit of all Canadians; and identify reimbursement possibilities for developing novel therapies..
Keynote speaker Dr Janet Rossant, President & Scientific Director of the Gairdner Foundation and Chair of the steering committee of the Council of Canadian Academies Workshop on Regenerative Medicine. Their soon-to-be-released report was commissioned by the federal government.
As well, speakers from the United Kingdom, Japan and California will discuss steps taken in their jurisdictions to move the science from the researchers’ laboratories to the patients’ bedsides.
“It is the medicine of the future,” says Dr. Alarco. “We hope to have action items in for this to become a reality for Canadians.”
Think of cancer immunotherapy as an inside job: While chemotherapy and radiation destroy cancer cells from the outside, cancer immunotherapy deploys the patient’s own immune system to attack the disease from within.…
Think of cancer immunotherapy as an inside job: While chemotherapy and radiation destroy cancer cells from the outside, cancer immunotherapy deploys the patient’s own immune system to attack the disease from within.
Cancer immunotherapy’s arsenal of immunotherapies ranges from monoclonal antibodies that can target malignant cells, inhibitors that help the immune system recognize and attack cancer cells, vaccines that trigger an anti-cancer response, and re-engineered and expanded T-cells designed to kill specific cancer cells.
For patients, the life-enhancing prospects of not having to endure the toxic side-effects of chemo and radiation are almost as appealing as the life-saving cures that this revolutionary field of oncological research is poised to deliver.
”The evidence suggests we are at the beginning of a whole new era for cancer treatments,” Prof. Peter Johnson, Director of Medical Oncology at Cancer Research UK, told the Daily Mail in 2015. Things have only accelerated since then for The Next Big Thing in cancer care.
The cancer immunotherapy revolution is moving fast and turning the oncology world upside down, according to Dr. Lambert Busque, Chief Medical Officer of the Centre for Commercialization of Cancer immunotherapy (C3i). Established last year by Canada’s Networks of Centres of Excellence, C3i predicts that immunotherapy could be used in the majority of advanced cancer cases in less than a decade.
Which raises the question: is Canada ready for this revolution in cancer care?
“There is a lot of knowledge and competence in Canada,” says Dr. Busque, whose C3i organization operates out of the Hôpital Maisonneuve-Rosemont’s Integrated University Center of East Montreal. But, he says, Canada needs greater capacity to translate immunotherapies into patient care and to help Canadian companies compete in a rapidly growing global market.
To address those concerns, C3i is partnering with CellCAN Regenerative Medicine and Cell Therapy Network and BioCanRx to host next month’s PanCanadian Strategic Forum on Cell and Gene Therapy in Montreal. Dr. Busque will moderate a panel discussion on what it will take for Canada to become a world leader in commercializing cancer immunotherapy, drawing on the C3i model.
“We designed C3i to be very close to the clinic,” says Dr. Busque. “Because treatment and health care is part of the public sector while development is done in the private sector, the key is to make the link between them, to have a structure to help Canadian inventions mature rapidly and have better access to markets. If we have no instrument to do that, the development will go outside the country.”
Canada, in fact, could become a hub for cancer immunotherapy development if 3Ci can succeed strengthening collaborations with major pharmaceutical firms in driving clinical trial development. Dr. Busque cites C3i’s access to a “state of the art” certified Good Manufacturing Practice (GMP) cell manufacturing unit as critical for conducting trials and developing cell-based and biological therapeutics.
C3i is also making the development of biomarkers a priority. Because not all cancer patients respond in the same way with the same immunotherapy, researchers worldwide have focused their attention on developing biomarkers that can predict therapy outcomes and help doctors tailor treatments to a particular patient or type of patient.
“Biomarkers will be crucial in the development of therapies,” says Dr. Busque. “So we are developing a biomarker unit with next generation computer sequencing to do cutting edge analysis of cellular biomarkers.”
Having already built a network of oncology centres across Quebec, C3i hopes to create linkages across Canada to expand access to patients for larger scale clinical trials.
“We’re not alone. We’re going to be one piece of a large puzzle in Canada. There are so many great contributions being made across Canada. We hope to be a catalyst in respect to Canadian collaborations because Canada can be extremely successful.”
Sometimes popular recognition takes time. After more than 50 years, Drs. James Till and Ernest McCulloch are finally getting their moment in the spotlight of public appreciation.…
Sometimes popular recognition takes time. After more than 50 years, Drs. James Till and Ernest McCulloch are finally getting their moment in the spotlight of public appreciation.
The Globe & Mail’s ongoing Great Canadian Inventions series, which highlights people, products and discoveries that have changed the world, today features the two great men who proved the existence of stem cells back in the early 1960s. The series runs throughout 2017 to mark the 150th anniversary of Confederation.
The Globe’s public health reporter André Picard reports that the discovery “is considered among the most seminal medical findings of the past century, on par with the discovery of the double-helical structure of DNA by James Watson and Francis Crick.”
Stem cells have revolutionized cancer treatment and set the stage for the emergence of new therapies for a wide range of currently incurable diseases. New treatments are already succeeding in overcoming autoimmune diseases like MS.
Stem cells are also good for the economy. The article cites STEMCELL Technologies, the Vancouver-based biotech company founded by former Till & McCulloch postgraduate student Dr. Allen Eaves, as a key player in a burgeoning field that is expected to produce a $49-billion global market within four years.
James Price, President & CEO of the Canadian Stem Cell Foundation, notes in the Globe piece that the Till & McCulloch discovery initially didn’t get the attention it deserved. “But they set the stage for all the current stem cell research and helped make Canada a magnet for talent and investment in biotech.”
The article comes after last fall’s unveiling of the Till & McCulloch statue outside doors of BC’s Telus Science World in Vancouver. A duplicate statue is to be installed in downtown Toronto this spring. It marks a considerable turnaround in recognition. In 2004, CBC Television ran a series called The Greatest Canadian, compiling a list of the 100 greatest Canadians ever. They followed it with a 2007 series on 50 of the Greatest Canadian Inventions. While Don Cherry was featured in the former and the Wonder Bra in the latter, Till & McCulloch and stem cells were left out of both.
The Globe series, however, got right to it in recognizing Till & McCulloch: they are the second Canadians to be featured this year after a Jan. 9th article celebrated how Jacques Plante changed the game of hockey by popularizing the goalie mask.
Dr. Till, a professor emeritus at the University of Toronto, remains busy as a leading advocate for opening access to scientific journals. Dr. McCulloch died in 2011. The remarkable story of Till & McCulloch’s stem cell discovery and their amazing legacy is told in Dreams & Due Diligence, published by University of Toronto Press and available through their website or via Amazon books.
In this blog and in our Fall/Winter newsletter we told the story of Dan Muscat, the St. Thomas, Ontario jeweler who has seen remarkable reductions in the symptoms of his scleroderma — a painful and deadly disease that turns the skin of its victims into cement-like hardness and then petrifies their internal organs.…
In this blog and in our Fall/Winter newsletter we told the story of Dan Muscat, the St. Thomas, Ontario jeweler who has seen remarkable reductions in the symptoms of his scleroderma — a painful and deadly disease that turns the skin of its victims into cement-like hardness and then petrifies their internal organs.
Over the summer, Dan underwent an experimental stem cell therapy at The Ottawa Hospital under the care of Dr. Harry Atkins, who has done outstanding work in treating patients with other autoimmune diseases such as multiple sclerosis, Stiff Person’s Syndrome and Crohn’s disease using a combination chemotherapy/stem cell approach.
Avis Favaro reported on Dan’s “180-degree” turnaround on CTV National News last night, telling Dan’s powerful story. You can watch it here.
After the initial report, the CTV website provides a four-minute interview with Dan that goes into greater detail, along with interviews with Dr. Atkins and James Price, President and CEO of the Canadian Stem Cell Foundation, who says “Dan’s story is an exciting one for the field.”
As Ms Favaro says at the end of her report, Dan continues to get improve and is now able to walk three kilometres on a treadmill. While the extreme treatment isn’t for all scleroderma patients — it comes with potentially fatal risks — it offers new hope where none existed before.
In the wake of the CTV story on Dan, The Ottawa Hospital has produced an online resource for people seeking more information about chemo/stem cell treatments for scleroderma and other autoimmune diseases like MS and Stiff Person’s Syndrome. You can find it here.
Researchers at Princess Margaret Cancer Centre in Toronto have developed a test to predict responses to standard treatments in patients with acute myeloid leukemia (AML) — one of the most deadly and common types of adult leukemia.…
Researchers at Princess Margaret Cancer Centre in Toronto have developed a test to predict responses to standard treatments in patients with acute myeloid leukemia (AML) — one of the most deadly and common types of adult leukemia.
The test is designed to be administered in tandem with diagnosis so that once the marker is identified, an individual treatment plan can be prepared.
“Clinicians will now have a tool that they can use upfront to tailor treatment to risk in AML,” says Dr. Jean Wang, Affiliate Scientist at the Princess Margaret and Co-Principle Investigator of the study in a press release from the University Health Network.
The marker identifies a 17-gene signature derived from leukemia stem cells that are resistant to standard chemotherapy and cause relapse for patients. Based on a rigorous statistical approach, a “stemness score” measures a patient’s probability for chemo resistant cells. With this knowledge, clinicians will be able to enroll high-risk patients in clinical trials to test alternative therapies to chemotherapy alone.
The test not only provides a fast turnaround time for patients as they decide the best course of care, it also represents the first time a stem cell-based biomarker has been developed in this way for human cancer.
The announcement by Bayer AG and Versant Ventures that they will invest $225 million U.S. to create a Toronto-based cell-therapy company shows the massive opportunities to be realized in the next wave of stem cell R&D and illustrates how visibility and support for the sector is soaring.…
The announcement by Bayer AG and Versant Ventures that they will invest $225 million U.S. to create a Toronto-based cell-therapy company shows the massive opportunities to be realized in the next wave of stem cell R&D and illustrates how visibility and support for the sector is soaring.
“We think we’re on the cutting edge of the next generation of stem-cell therapies,” said Brad Bolzon, Managing Director of Versant Ventures in a report by the Globe and Mail.
According to Bayer’s press release, the new company, called BlueRock Therapeutics, will advance breakthrough treatments based on latest stem cell technology with an initial focus on finding treatments for cardiovascular diseases and neurodegenerative disorders like Parkinson’s disease, two areas where Canadian research is particularly strong. The investment, one of the largest-ever first-round financings for a biotech company, gives BlueRock Therapeutics at least four years to get a number of programs into the clinic.
It comes in the wake of several developments including the Stem Cell Network’s announcement of $9 million in funding for projects to turn research into new treatments and the Canada First Research Excellence Fund’s $114-million grant to the University of Toronto’s Medicine by Design program. As well, the Centre for Commercialization of Regenerative Medicine announced earlier this year that it will receive $20 million in federal funds, matched by GE Healthcare, to develop cell manufacturing capacity in Canada.
“All of these announcements align with the Canadian Stem Cell Strategy’s goals of mobilizing private capital and attracting investment,” said James Price, President and CEO of the Canadian Stem Cell Foundation. “They are strong indications that Canada is well positioned to lead in the next wave of stem cell advances. That’s why we’re seeking a commitment from the Liberal Government to make stem cell research and development a national priority.”
The Canadian Stem Cell Strategy is designed to deliver 10 new therapies to the clinic within 10 years, create 12,000 jobs and position Canada as a global leader in the field. It calls on the Government to provide one-third of the total investment, about $50 million annually over 10 years for a total of $500 million, to be doubled by $1 billion in private and philanthropic investments.
An indication of the economic power of stem cell R&D is exemplified by BC’s STEMCELL Technologies Inc., which, with 900 workers and $150 million in annual revenues, has become Canada’s largest biotech by selling high-quality “Made in Canada” stem cell products worldwide.
“We have a huge opportunity in front of us, an opportunity we don’t want to miss,” said Mr. Price. “Visibility and support for the sector has never been stronger. We just need to take the next big step forward with the Strategy.”
Unveiling its 2016 funding awards last week, the Stem Cell Network announced support for six clinical research trials for new cell-based treatments.…
Unveiling its 2016 funding awards last week, the Stem Cell Network announced support for six clinical research trials for new cell-based treatments.
“The regenerative medicine research sector is fueled by stem cells and today it is at a tipping point, with the potential to see breakthroughs in our generation,” said Dr. Michael Rudnicki, Scientific Director of the Stem Cell Network.
One of the big winners was Dr. Lauralyn McIntyre, a researcher/clinician at The Ottawa Hospital and a professor at the University of Ottawa. Her team receives $1 million of the $9 million in announced funding to conduct a cross-Canada Phase 2 clinical trial of mesenchymal stem cell therapy for septic shock. We profiled her work on the deadly condition here.
Her colleague at The Ottawa Hospital, Dr. Duncan Stewart, will use his $999,546 award to advance his work testing enhanced angiogenic cell therapy for acute heart attacks. Check out Dr. Stewart’s Q&A here.
As well, Dr. Sandra Cohen at the Hôpital Maisonneuve Rosemont in Montreal will investigate ways to improve the expansion of cord blood hematopoietic stem cells via her $999,968 award.
Two diabetes trials were also funded: Dr. Timothy Kieffer of the University of British Columbia gets $500,000 to test a stem cell therapy for insulin replacement, while Dr. James Shapiro of the University of Alberta receives almost the same amount for a clinical trial to solve the “supply and survival problem” in using stem cell transplants. Both Dr. Kieffer and Shapiro also receive $500,000 in funding through the Network’s Disease Team Program.
In all, 31 projects from across Canada will receive funding to help move research from lab bench to bedside in areas such as brain injury, kidney disease and breast cancer.
Making the announcement, Science Minister Kirsty Duncan said the investment will help translate discoveries into better health and economic growth for Canadians. It was made possible with the announcement of a two-year, $12-million extension of the Stem Cell Network in the March federal budget.
In a news release, Dr. Stewart said the funding “brings us a big step closer to figuring out how to harness the incredible potential of stem cells to treat devastating diseases.”
In the summer of 2014, Dan Muscat’s fingertips started to tingle. It felt like tiny shards of glass were piercing the skin underneath his fingernails.…
In the summer of 2014, Dan Muscat’s fingertips started to tingle. It felt like tiny shards of glass were piercing the skin underneath his fingernails. Over the next weeks and months the pain crept into his hands.
His family doctor thought it might be arthritis and prescribed a steroid to get things under control. “Within days, the disease sped up,” says Muscat. “It went from the top of my head to my toes. My ankles and my feet were so inflamed I couldn’t walk 20 feet.”
Muscat, who owns a jewelry business in St. Thomas, Ontario, was referred to a rheumatologist who immediately recognized what was happening to him: “Dan had rapidly progressive early onset diffuse scleroderma,” says Dr. Janet Pope of St. Joseph’s Health Care in London.
Scleroderma — from the Greek words for “hard” (sclera) and “skin” (derma) — is the term used for a group of rare autoimmune diseases that, according to the Mayo Clinic, involve hardening of the skin and connective tissues due to an overproduction of collagen. Diffuse scleroderma is a systemic type of the disease, meaning it affects not only the skin and muscle but also the digestive tract and internal organs, ultimately leading to death.
The future did not look good for Muscat: “He had not responded to usual immune suppressive treatment,” says Dr. Pope.
By late 2015, Muscat was growing desperate. He had heard that Dr. Richard Burt at Northwestern University in Chicago was offering a treatment using a patient’s own bone marrow stem cells to rebuild their immune system and shut down scleroderma. Muscat reached out to the Canadian Stem Cell Foundation for guidance.
“I investigated costs of Northwestern University treatment,” says Muscat, “and it was somewhere between $300,000 and $350,000. I thought about selling my business or my home. If I had to, I would have done that. Financially, it would have been a huge burden.”
Because the American treatment is similar to the combination chemotherapy/ bone marrow stem cell transplant treatment that The Ottawa Hospital’s Dr. Harry Atkins has used successfully against extreme forms of multiple sclerosis (MS, which is also an autoimmune disorder), the Foundation suggested Muscat reach out to him. Earlier this year Dr. Atkins agreed to take Muscat on as his first scleroderma patient.
“He fit the profile of the kind of patient best treated with these kinds of stem cell transplants” says Dr. Atkins, who is also an associate professor at the University of Ottawa. “There was a randomized trial carried out in Europe that was very well done and had very good results. I know the doctors involved and we’d talked a little bit about it, but their methods had also been published and are available for everybody. That’s why we publish — to spread the knowledge.”
By the time Muscat arrived in Ottawa in May, the disease had taken its toll. Once an imposing figure who worked out regularly and thought nothing of going for five- or six- miles runs, Muscat had watched 45 pounds fade from his six-foot frame. His brisk walk had turned into a painful shuffle. His boundless energy (he built a log home by himself, is an avid fisherman and collects classic sports cars) disappeared, making it difficult to get through a day. His fingers became like stone claws, curving in at the knuckles. His skin was so impenetrable he worried the Ottawa medical team might not be able to run an intravenous line. And the pain was excruciating.
“On a scale of 1 to 10, about 15,” Muscat says.
Muscat began the therapy in June and spent much of last summer undergoing the treatment designed to destroy the diseased immune system and rebuild it with his own purified stem cells, ideally to produce a new, scleroderma-free one. Though not as harsh as the chemotherapy MS patients undergo, it is not a treatment to be taken lightly. The risk did not dissuade Muscat: “If the treatment didn’t kill me, the disease would.”
He made it through chemo with few noticeable side-effects beyond losing his hair and tolerating a couple of infections. Released from hospital in August, he embraced physiotherapy, doing three to five hours daily to get his flexibility back and rid his body of the collagen buildup.
He is now back in St. Thomas, occasionally working at the store — he has to limit his time in public places because the chemo has left him vulnerable to infections. “My pain is one or two percent compared to what it was before.” His range of motion with his arms and legs is much improved and he can get around on foot again.
He realizes it could take a year before the chemo drugs fade from his system and the full benefits of the treatment kick in. Muscat, grateful for the excellent care provided by The Ottawa Hospital’s bone marrow transplant team, is unswerving in his belief that he can beat this disease. “I feel physically and mentally better. I just don’t feel that I’m being attacked.”
In an email message, rheumatologist Dr. Pope said that while Muscat “has a long road ahead, we expect more recovery with softening of his skin and improved function. His pain is less and he feels that shortly after the transplant a ‘switch’ was turned back to how it should be and he developed a better sense of well-being. I will follow him carefully and I hope for more improvement over the next year or two. He is in physiotherapy and is getting ongoing intravenous drugs for safety as his immune system continues to reconstitute. I am very hopeful that Dan will be even better over time. This is not a cure, but has given Dan a better chance of recovery.”
In Ottawa, Dr. Atkins also urges caution. “It’s going to take months and months to know if this is a real improvement. The changes with scleroderma don’t happen overnight. This is not a curative treatment; it doesn’t make scleroderma go away and never come back. It’s something that helps a population of scleroderma patients: some patients improve, some not. There are patients that progress or relapse again.”
Muscat is positive about the future: “I still have the remnants of the disease, but I can jump in and out of my truck again and I can walk a couple of kilometres with no problems. I feel very optimistic, like I’ve been given a second chance.”
We can add another disease to list of conditions that can now be treated with bone marrow stem cell transplants: myasthenia gravis (MG).…
We can add another disease to list of conditions that can now be treated with bone marrow stem cell transplants: myasthenia gravis (MG).
This week, CTV News in Ottawa told the story of Anne Scott, a 58-year-old Kemptville, Ontario woman whose MG refused to respond to conventional therapies.
MG is an autoimmune disorder like multiple sclerosis (MS). It interrupts communication between the muscles and the nerves, which can make swallowing and breathing difficult.
While most patients can be treated with conventional therapies, some, like Scott, cannot. She had to be placed on life support a dozen times.
Under the supervision of The Ottawa Hospital’s Dr. Harry Atkins, Scott underwent a chemotherapy/stem cell procedure. Essentially, it involves one using a patient’s own blood stem cells to rebuild their immune system after it has been wiped out by chemo therapy. If all goes well, the rebuilt immune system is free of the disease.
Dr. Atkins has had success using this approach to treat patients with MS, Stiff Person’s Syndrome, neuromyelitis optica and Crohn’s disease. The procedure has been used to treat leukemia and other forms of blood-based cancer for decades.
Scott, who was able to attend her daughter’s wedding shortly after undergoing the procedure, was one of seven patients in a study led by Dr. Atkins, the results of which have been reported in in JAMA Neurology All seven patients no longer need treatment for MG and are symptom-free.
You can find out more about the study here.
Dr. Paola Marignani is searching for new treatments. More precisely, the Dalhousie Medical School researcher wants a new combination of drugs to target cancer in a new and different way.…
Dr. Paola Marignani is searching for new treatments. More precisely, the Dalhousie Medical School researcher wants a new combination of drugs to target cancer in a new and different way.
“Many of the drugs we have in the clinic today block oncogenes that were discovered 15 or 20 years ago,” says Dr. Marignani, pictured at right. “We can’t just keep using the same drugs over and over again in different combinations. We need to find new targets and new drugs.”
Her key target is LKB1, a protein that has multiple functions throughout the body, including tumour suppression. LKB1 is often found to be missing or mutated in breast cancer, lung cancer, pancreatic cancer and other forms of the disease. “If you lose LKB1 or its mutated, it sets up protein signalling pathways for disaster,” says Dr. Marignani. “It would be like an intersection that once had stop signs and is now without any. Eventually an accident is going to happen.”
To understand what happens when LKB1 is lost and mutated, her team used re-engineered mice without the ability to express the protein. That led them to finding a combination of compounds that shuts down aggressive, metabolically active HER2-positive breast cancers — a common form of the disease — in the rodents.
Dr. Marignani is using a two-pronged approach by testing the new compounds in combination with Herceptin®, which has become the standard of care for HER2-positive breast cancer. “We know Herceptin® is effective,” says Dr. Marignani. “We can use the discovery we made in mice to strategically attack the cancers from multiple branches using new drugs in combination with the standard treatment of care, and see what happens.”
So far, she is cautiously optimistic. “The animals tolerate the drug combination, which is very important, and early data suggests the tumours are not progressing.”
Beyond shutting down tumour growth, Dr. Marignani and her team want to find ways to stop cancer from recurring by killing off the cancer stem cells that resist the original treatment.
“There is always the possibility that there are some cancer stem cells hiding out, just waiting, that have developed resistance to the treatment that killed off the bulk of the cancer,” she explains. “We have seen that our drug combination reduced the proteins that drive recurrence. We did not anticipate this would happen because there was no evidence in the literature. In our current study, we need to consider whether stem cells play a role in cancer recurrence in our model and look for pathways that are active in those cells. We don’t know yet. We’re working on it.”
With fine tuning of her animal-model preclinical work done, Dr. Marignani hopes to move into a Phase 1 clinical trial, testing the safety of the drug combination in humans. But she emphasizes that the work is in the early stages.
“It is important that we look for new treatment possibilities even though the current treatments are reasonably good. Targeting oncogenes has served us well, however it is time we expand our toolbox. We can do better.”