In the Spotlight

Ottawa Hospital Research Institute 2013–2014 Annual Report

Fixing a broken heart:
Making your stem cells young again

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On November 14, 2013, after seeing his wife off to work, Langis LeBel had an ominous feeling that the symptoms he had been experiencing — malaise, indigestion, jaw pain, sore left shoulder and chest pain — should no longer be ignored.

The retired OPP sergeant had seen heart attacks when he was on the job and said to himself, "Get with the program, buddy!"

It turned out that the 60-year-old had a blocked artery that ran down the front of his heart, often called a “widow maker.” Once he was rushed to hospital, doctors whisked him into the catheterization laboratory, opened up the artery with a balloon and put in a metal stent. Before he knew it, he was recovering in the intensive care unit.

LeBel was shocked when his attending physician told him that he was actually very lucky to be alive and that eight of 10 people with such a serious heart attack are not so fortunate.

Although still beating, LeBel's heart had suffered major injury. Such extensive damage leads to ongoing and progressive health complications resulting from a weakened and enlarged heart. This can lead to heart failure and, too often, premature and untimely death. Current heart-attack therapy is focused on opening up the blocked artery as soon as possible in an attempt to salvage heart muscle at risk. Once the damage has occurred, doctors can only wait to see how the heart heals and how the body copes with the heart's reduced ability to pump blood.

"It does change your life because there are so many things you can't do anymore," said LeBel.

Dr. Duncan Stewart and his team want to change this. They are conducting a world-first clinical trial that uses a revolutionary stem-cell therapy. The idea is to improve the heart's ability to heal itself using a person's own genetically enhanced stem cells.

"Using someone's own stem cells means that we avoid the problem of their body rejecting them," said Dr. Stewart, CEO and scientific director of the Ottawa Hospital Research Institute, vice-president of Research at The Ottawa Hospital, and professor of medicine at the University of Ottawa.

"However, the patient's own stem cells have reduced healing potential since they have been exposed to the same diseases and conditions that led to the heart attack in the first place. To rejuvenate these cells, we are inserting a small piece of genetic code that makes them more active and more effective in repairing the heart," added Dr. Stewart.

It's the first time gene-enhanced stem cells have been used to treat cardiovascular disease. To run this clinical trial, the Ottawa Hospital Research Institute built a clinical cell manufacturing facility that is unique in Canada. It was designed specifically to handle complex procedures, such as inserting the gene into stem cells and then preparing them for use in patients.

Time is also of the essence in this experimental therapy. The cells must be given back to the patient before the injured heart tissue scars and hardens, which takes about one month. As a result, the 100 participants in this trial will be treated between five and 30 days after their attack.

The trial's volunteers are randomly assigned to receive one of three treatments: a placebo, their own cells, or their own gene-enhanced cells. LeBel was still in the hospital when he was asked to participate in the trial. He jumped at the chance, even though he knew he only had a two in three chance of receiving stem cells.

For LeBel, those odds were definitely worth it.

However, he signed on to participate in the clinical trial for something more. "I feel strongly that it is something you need to do, otherwise we don't advance," said LeBel.

By participating in Dr. Stewart's research, he could be helping to usher in a new era of regenerative medicine.

"If this trial is successful," said Dr. Stewart, "it could open the door to therapies based on genetically enhanced stem cells that can restore function and reverse damage in other critical organs, not just the heart. It could give us ways to treat significant and devastating diseases for which we currently have no options, such as kidney failure, stroke and lung diseases."

Recognizing the potential of this critical research, The Ottawa Hospital Foundation has committed to raising $15 million for regenerative medicine to give our researchers the support and tools they need to bring promising results to patients as quickly as possible.

Dr. Stewart's trial is scheduled to finish enrolling patients by 2015.

Precise and personal cancer care:
Our genes hold the key

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Cancers have long been named for the part of the body where they originate, which is why Paula Helmer was shocked to find that the tumours removed from the bone in her neck were actually breast cancer.

“I didn’t have any lumps in my breasts, but the doctors told me it was breast cancer that had spread to my bones,” said Helmer.

What followed her unusual diagnosis was a personalized approach to cancer care that highlights how much the field has changed in this age of genetically informed medicine.

Dr. Mark Clemons, Helmer’s medical oncologist at The Ottawa Hospital Cancer Centre, is among a new generation of cancer specialists who are moving from prescribing drugs based on the tissue of origin, to the molecular basis of each patient’s cancer. By identifying the genetic flaws inside a tumour cell, Dr. Clemons is able to tailor therapies to a patient’s individual type of cancer, providing a more effective treatment. In fact, his research in this area is improving care for cancer patients worldwide.

With surgery and radiation therapy behind her, Helmer did not move on to the usual courses of chemotherapy. While chemotherapy may work for some patients, it often causes harmful side effects such as nausea, hair loss and organ damage.

“We’re now able to tell more and more of our patients, ‘I don’t think chemotherapy is going to help you. We've got a much less toxic treatment option to give you,’” said Dr. Clemons, who’s also a clinical investigator at the Ottawa Hospital Research Institute and a professor at the University of Ottawa.

“This personalized approach allows us to provide our patients with treatments that have the fewest side effects and the best possible outcome. We don’t waste precious time trying drugs that may not be effective for a patient.”

In Helmer’s case, Dr. Clemons ordered molecular tests that could predict which drugs would – and which would not – slow the progression of her particular type of cancer. The tests provided a detailed profile of the specific genetic flaws causing the tumour cells inside Helmer to grow. Dr. Clemons then matched this information with specific drugs able to target her cancer.

In that way, Helmer has received kinder, gentler drugs that have allowed her to live longer and better than even Dr. Clemons thought was possible. More than four years after her diagnosis, Helmer continues to travel, sing in a choir and enjoy quality time with her husband, children and grandchildren.

“I’m enjoying my life and I count my blessings every day,” she said.

Through personalized medicine, Dr. Clemons has reduced the frequency and dose of the drugs given to Helmer without compromising their effectiveness.

Indeed, Helmer was part of a research study led by Dr. Clemons. The study found that women who had low levels of a certain blood marker could benefit from taking a drug less frequently to treat breast cancer that had spread to the bone.

Dr. Clemons and his collaborators discovered that less frequent treatments – once every three months rather than once every month – were just as effective. They also resulted in fewer side effects and reduced drug costs. The finding has already changed the way cancer centres around the world treat women with advanced breast cancer.

The personalized approach has also allowed Dr. Clemons to prescribe different drugs for Helmer as her cancer cells have continued to evolve and behave differently over time. His research has demonstrated that women with advanced or recurring breast cancer benefit from having an up-to-date biopsy to determine if their treatment plans should be changed. That’s because four out of 10 women with recurring breast cancer have tumours with a different molecular profile compared to that of their original tumour.

Because of this finding, it’s now considered best practice for oncologists to check the molecular profile of breast cancer that has spread or returned before giving patients the same treatments they previously received.

Dr. Clemons' finding serves as a reminder of how devilishly complex cancer is and how much more remains to be understood. That’s what motivates Helmer to participate in many of Dr. Clemons’ research studies.

“I have received excellent care at the hospital and this is my way of giving back,” she said. “I’ve benefitted from the people before me who made the effort to join these studies. I want to do whatever I can to move the research along so that other people will benefit down the road.”

Given the promise of personalized cancer therapy, The Ottawa Hospital Foundation is working to raise $3 million to establish an Oncology Diagnostics Laboratory, allowing Ottawa residents to benefit from quick results for the most advanced molecular testing.

Beyond hysterectomy:
New options give women their lives back

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It’s rare to find a woman who has never had any trouble with her period. For most women, the hassles are fairly minor. But for Natalie Reesal, who suffered from crippling pelvic pain and abnormally heavy bleeding that would last for weeks, her menstrual cycle put life on hold every month.

“The pain was so severe that probably two out of the three days of my cycle, I was on the bathroom floor because that was the only relief I could feel from the pain,” said Reesal.

She was diagnosed with non-cancerous tumours in the uterus, known as fibroids, as well as a severe form of endometriosis, in which tissue usually found in the lining of the uterus grows outside of it.

In the past, the only treatment available for women with Reesal’s diagnoses was an invasive hysterectomy, which removed the uterus and sometimes other reproductive organs as well. The surgery was particularly devastating for women of child-bearing age because it robbed them of any chance to have children. Reesal, for one, still held out hope of starting a family with her husband, even though she was warned that the odds were against it.

Dr. Sony Singh does not believe that a woman should have to choose between suffering and a surgery that leaves them infertile. “Women are having children later in life,” he said. “Those with endometriosis or fibroids don’t want hysterectomies if they can avoid it.”

As director of the Shirley E. Greenberg Women’s Health Centre at The Ottawa Hospital and a clinical investigator with the research institute, Dr. Singh is known for his expertise in treating the one in 10 women who are diagnosed with endometriosis. His program also treats the four in 10 women whose abnormal bleeding stems from non-cancerous cysts, lesions and fibroids. His pioneering work has inspired Ottawa-area residents to donate $1 million in support of his program.

Dr. Singh specializes in alternatives to hysterectomy, such as minimally invasive surgical methods to remove the growths while preserving the uterus. He also uses techniques that shrink or kill the growths by cutting off their blood supply. These techniques have helped some patients avoid surgery altogether.

Using those surgical methods, Singh was able to give Reesal her life back. She eventually gave birth to a healthy girl. “She’s just a miracle. She has just brought so much joy in our lives.”

Another benefit of minimally invasive gynecology is faster recovery time. Nine out of 10 patients who have surgery under Dr. Singh’s program go home in less than 24 hours. Since the program started nearly a decade ago, fewer women have remained as inpatients to recover from hysterectomies, saving the equivalent of five years of hospital stays.

One of these women is Antonette Deza. A native of the Philippines, Deza had been in Canada for only a few months when she learned that, because of endometriosis, she had a large, non-cancerous tumour pressing against her bladder.

Under Dr. Singh’s care, Deza had a laparoscopy. Tiny incisions, no more than a centimetre long, were made in her abdomen and a camera was inserted to accurately diagnose and treat her condition. When she woke up from the surgery, Dr. Singh told Deza he had removed the tumour while keeping her uterus intact. “I'm still young and I want to have children so I was very happy,” said Deza.

Dr. Singh sees many women like Deza who are in advanced stages of disease, but suffer in silence because they fear that major surgery is their only option. Many of them are either newcomers to Canada, or from under-served cultural communities where there’s a stigma or lack of awareness about women’s reproductive health.

With a multilingual team of surgeons and trainees, Dr. Singh and his colleagues treat many women who would otherwise fall through the cracks of the health-care system. Indeed, as only the second Canadian centre to be internationally recognized as a training ground for minimally invasive gynecology, The Ottawa Hospital attracts a multicultural team of surgical fellows from across the country.

“Collectively, our team speaks English, French, Cantonese, Mandarin, Persian and Punjabi,” said Dr. Singh, who is also an associate professor at the University of Ottawa. “We’re not only training the next generation of specialists with the most up-to-date surgical skills; we’re also training people who reflect the cultural diversity of this country. They can reach out to communities that are currently underserved, so that women of all backgrounds no longer have to suffer in silence. We can give them their lives back.”

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Copyright 2014 Ottawa Hospital Research Institute

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