Research from the UBC School of Medicine could stop the disease in its tracks — and even reverse its devastating effects
One day in the spring of 2014, Heidi Scott’s face went numb. Out of nowhere, just-back-from-the-dentist numb, as she vividly remembers.
“I was on a business trip and it took me completely by surprise. My whole face was affected,” says Heidi.
Alarmed, she returned home to see her doctor, who ordered a battery of tests. The results were inconclusive.
Heidi was in her early forties, a runner, and in good health. Her doctor said she could expect a full recovery, and she eventually did. After a month or two, she regained feeling in her face.
“After I got back to normal, the incident felt kind of unreal, like did this really happen to me?” she says.
A year later the numbness returned. This time it spread through Heidi’s ear, down her neck and into her shoulder. There were muscle spasms and periods of extreme fatigue. An ear infection is ruled out, as well as various nerve problems. Again the symptoms disappeared and once again Heidi was left wondering what was going on.
Within a few weeks, she began to struggle with balance and coordination and slurred speech. Heidi worried that her coworkers might think she was drinking. She also worried that people thought the problem was in her head because the symptoms came and went. They were unpredictable.
“If we can stop the progression of the disease and help people regain even a fraction of what they’ve lost, the impact on their quality of life will be quite profound.”
— Dr. Freda Miller, Professor of Medical Genetics
An MRI finally confirmed that something was indeed wrong. The scanner revealed small lesions, or “scleres,” in the white matter of her brain. She was referred to the Vancouver Coastal Health MS Clinic at the UBC Faculty of Medicine’s Djavad Mowafaghian Center for Brain Health.
After careful consideration of her symptoms and test results, doctors diagnosed her with multiple sclerosis (MS). MS is a progressive autoimmune disease that attacks nerve cells in the brain and spine, causing a bewildering array of symptoms.
At the MS Clinic, Heidi was able to receive treatment that helped control her symptoms and slow the progression of the disease. Unfortunately, like most MS drugs, it is a powerful immunosuppressant that makes her vulnerable to infections. Even a mild illness like a common cold can be dangerous.
But there is reason for optimism. New technologies and new research are opening up new treatment and care options for MS.
“We are truly in the midst of a golden age of biomedical innovation,” says Dr. Peter Zandstra, a professor in the UBC School of Biomedical Engineering (SBME) and an expert on stem cells and bioengineering.
“It’s exciting because the ultimate goal is to get patients’ lives back.”
Researchers at the UBC School of Medicine are working across disciplines to do just that. They are developing new therapies to control MS symptoms for more patients with fewer side effects, slow the progression of the disease — and even reverse the damage it causes to the nervous system.
And thanks to a new gift – the largest known endowment for MS research worldwide – UBC is poised to become a global center for MS innovation, expanding its team science approach to bring new and better therapies to patients earlier than ever.
For the more than 90,000 Canadians living under the shadow of MS — and the 4,000 who receive a diagnosis each year — sooner can’t come soon enough.
Stopping a debilitating illness
It is the unpredictability of the disease that makes MS so difficult to diagnose, treat and live with.
MS attacks and destroys myelin, the fatty sheath that covers nerve cells in the brain and spine. If you think of nerve cells together as the wires along which information (in the form of electrical signals) travels through the nervous system, then myelin is the protective coating that insulates the wires, allowing information to flow smoothly from place to place without interference. Your brain sends a message to your eyelid telling it to blink, and it does, quite simply.
As the myelin disappears, the nervous system begins to malfunction. Because MS attacks nerve cells seemingly randomly, people with the disease can experience a wide range of symptoms. In a person, this can disrupt communication between the brain and the optic nerve, causing vision loss. In another case, it can disrupt the function of the bladder or cause severe numbness in the hands and feet, even paralysis.
Symptoms come and go, especially in the early stages and especially in patients with the relapsing-remitting form of the disease, like Heidi Scott. If left untreated, the disease can progress even during periods of apparent remission.
Today’s treatments are changing lives in good and bad ways. For Heidi, they allow her to live almost symptom-free with the confidence that the disease is not quietly destroying her nervous system. But they also mean giving up the social life that most people take for granted.
“I’m happy that I work from home, so it’s easier for me to avoid everyday viruses that can make me very sick. But the side effects of the treatment had a huge impact. Not everyone understands the consequences of immune deficiency. I’ve had fights with loved ones because I have to isolate myself,” she says.
It’s a tough trade-off, and even then, current treatments don’t work for everyone. For many patients, MS still means debilitating daily symptoms and long-term disability.
Dr. Megan Levings, a professor in UBC’s Department of Surgery and SBME, has developed a cell therapy that promises to make immunosuppressive treatments more effective for more people. She leads a team of immunologists and cellular engineers who have demonstrated that it is possible to “train” regulatory T cells (Tregs) – a type of immune cell that controls the body’s response to healthy tissue – to recognize and accept specific types of tissue that otherwise, a malfunctioning immune system may attack.
“We want to do for MS what was done for cancer,” she says. “We know, for example, that certain types of T-cell therapies can be used to help the immune system fight cancer and infection. With MS, we want to reduce the body’s immune response that leads to disease.
The goal is immunotherapy to control the specific and unwanted inflammatory response that leads to demyelination in MS — while allowing the immune system to function normally in all other respects. The hope is that MS patients will one day enjoy the benefits of current treatments with few or no side effects.
Thanks to the innovative bioprocess engineering techniques developed by Dr. Zandstra and other bioengineers, the therapy, if successful, could be produced at scale more easily than most therapeutics, making it quickly and widely available to patients as an off-the-shelf treatment.
Dr. Anthony Trabulzi (left) consults with a patient at the VCH MS Clinic at UBC Hospital.
Repairing the brain — and restoring quality of life
For many MS patients, the greater concern is restoring the neurological function they may have already lost.
“It breaks my heart to see patients I’ve known since their diagnosis suffer from serious, progressive disabilities due to the current lack of treatment options,” said Dr. Anthony Trabulsi, UBC clinical professor and neurologist at the MS Clinic.
Regenerative medicine may hold the key.
Dr. Freda Miller, a UBC professor and renowned neurobiologist in the Department of Medical Genetics, is leading a multidisciplinary team of scientists at UBC and Sick Kids Hospital in Toronto investigating the use of stem cells to repair the damage caused by MS.
Stem cells are the precursors to the specialized cells that the body needs to function. Whether a stem cell will develop into, for example, a blood cell, an immune cell or a neuron depends on the signals it receives from the environment, in the form of chemical messages from the network of cells that surround them.
“The beauty is that the brain contains reserves of neural stem cells. With the right chemical cues, they can be turned into cells that produce myelin, replacing those destroyed by MS,” explains Dr. Miller. “If we can understand what those cues are, we can stimulate the brain to repair itself.”
But to decode the messages that drive a stem cell to become a myelin-producing cell, you have to cut through the noise of all the other communication going on in the cell’s environment—a daunting task that requires multidisciplinary expertise and involves massive amounts of data.
This is where the team science approach makes the difference.
Dr. Miller also works closely with Dr. Zandstra. Neuroscientists in her lab collaborate with his team of physicists and biomedical engineers to model cellular networks in three-dimensional space, which they use to formulate and test predictions about cell behavior. Together, the teams are creating a map of cellular communication networks that could lead to a breakthrough in the treatment of MS and other similar diseases.
“The beauty is that the brain contains reserves of neural stem cells. With the right chemical cues, they can be turned into cells that produce myelin, replacing those destroyed by MS.
— Dr. Freda Miller, Professor of Medical Genetics
Dr. Miller believes her team’s research, if successful, could work in tandem with Dr. Levings’ immunotherapy to give patients a chance at recovery.
“In a perfect world, we figure out a way to regenerate the damaged areas while our immunology colleagues train the immune system to leave the new myelin alone,” says Dr. Miller. “It’s a one-two…
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