Our UHN programs and services are among the most advanced in the world. We have grouped our physicians, staff, services and resources into 10 medical programs to meet the needs of our patients and help us make the most of our resources.
University Health Network is a health care and medical research organization in Toronto, Ontario, Canada. The scope of research and complexity of cases at UHN has made us a national and international source for discovery, education and patient care.
Our 10 medical programs are spread across eight hospital sites – Princess Margaret, Toronto General, Toronto Rehab’s five sites, Toronto Western – as well as our education programs through the Michener Institute of Education at UHN. Learn more about the services, programs and amenities offered at each location.
Maps & Directions
Find out how to get to and around our nine locations — floor plans, parking, public transit, accessibility services, and shuttle information.
Ways You Can Help
Being touched by illness affects us in different ways. Many people want to give back to the community and help others. At UHN, we welcome your contribution and offer different ways you can help so you can find one that suits you.
The Newsroom is the source for media looking for information about UHN or trying to connect with one of our experts for an interview. It’s also the place to find UHN media policies and catch up on our news stories, videos, media releases, podcasts and more.
Abby Congram, 17, has Rett syndrome, a rare neurological and developmental disorder that necessitates 24-7 assistance
In many ways, Abby Congram is a typical 17-year-old. She likes socializing with her friends, and she’s interested in boys and music (Great Big Sea and Meghan Trainor are her favourite artists). Abby also loves horses – there are pictures of horses all over her room, and she rides them near her home in Stratford, Ont.
But unlike most of her peers, Abby is unable to speak. She can’t use her hands to type or hold a pencil or eat. She needs 24-7 assistance for all the activities of daily living. Abby has Rett syndrome, a rare neurological and developmental disorder that affects girls almost exclusively.
One in 10,000 females around the world is born with Rett syndrome, a genetic disorder whose cause wasn't even known until 1999.
Because it's neurologically based, symptoms vary greatly, but they can include seizures, the inability to speak, irregular breathing, poor thermoregulation (maintaining proper body temperature), an irregular heart rate, problems walking and the loss of purposeful hand use. Abby suffers from painful gastrointestinal problems and muscle weakness, which are also symptoms typical of Rett syndrome.
"Abby's muscle tone will suddenly go low one day and she can't walk, when yesterday she could," says Karen Congram, Abby's mother. "She has a lot of difficulty with what's called the autonomic nervous system, which controls her digestive system and her heart rate and her bladder, and so when the nervous system decides it's not working today, that creates a lot of pain."
Though Abby has been able to adapt to life with Rett syndrome – she attends classes with her peers at her local high school, and she's been learning to express her thoughts by using a special "eye gaze" communication device – Ms. Congram explains that kids with Rett syndrome often spend years unable to tell the world how they feel.
"These girls spend so many days in pain, and it's trying to manage that pain without having really specific communication about where it's hurting," she says. Ms. Congram and Abby have met many families of girls with Rett syndrome through her work on the board of the Ontario Rett Syndrome Association.
"For a lot of our girls, there are seizures or breathing problems. We have friends with kids in hospital on respirators because the breathing is controlled by your nervous system."
Rett syndrome is a disorder without a cure or any effective treatments to curb its debilitating and painful symptoms. But Dr. James Eubanks is working to change that.
Dr. Eubanks is a senior scientist at the Krembil Research Institute, and he's dedicated the last 15 years of his career to unravelling the mysteries of Rett syndrome. He recently received a research grant from the Ontario Rett Syndrome Association to aid in his team's hunt for drugs that can overcome the genetic mutations found in Rett syndrome. While the ultimate goal of research is to find a cure, Dr. Eubanks says, he and his team are also investigating whether drugs can be identified that could reduce or eliminate specific symptoms.
"Can we do something that will get rid of their epilepsy? Can we make their breathing better? Can we make their gastrointestinal difficulties better?" says Dr. Eubanks. "Can we find something that will make them speak again? We think these are achievable goals."
Dr. Eubanks met Abby more than a decade ago at a Run for Rett fundraiser when Abby was six years old. It was the first time Dr. Eubanks had met someone with Rett syndrome, and he invited Abby and her family to come to his lab. In the years since, she and her mother – along with other Rett syndrome kids and families – have visited Krembil multiple times.
"Abby definitely has a special bond with Dr. Eubanks; she recognizes him every time she comes back," says Ms. Congram.
Dr. Eubanks says that getting to know people like Abby is highly motivating for him and his team at Krembil.
"If you're working on a condition, it's important to know people who have the condition," he says.
"One of my students was [working on a drug] and one day she came in really, really excited and said, 'I got the [drug] to work.' And I said, 'Very good. But are you sure enough that you'll be willing to give that drug to Abby?' And she said, 'Not yet.' And I said, 'Come back when you're sure. There's still a long way to go.' And that's why it's so important," explains Dr. Eubanks. "It's one thing to find a drug and say, 'This is great,' but then when you actually know the person that the drug is going into, it gives you a little bit more impetus to get it right."
The search for disease-improving strategies stems from a groundbreaking discovery that showed even the worst neurological problems seen in Rett syndrome can be
rescued in experimental genetic models. These genetic models have the same mutation of the gene called methyl-CpG binding protein 2 (MECP2) that causes Rett syndrome in 90 per cent of the people who have the disorder. The MECP2 gene is important because it provides instructions for creating a protein that is critical for normal brain function. Mutations of this gene prevent the protein from being made, and this causes problems in the brain.
Using these genetic models, Dr. Eubanks' group showed clearly that if the missing or non-functional MECP2 gene is reintroduced, many of the existing neurological problems can not only be improved, but also in some cases completely returned to normal. "The experimental results show unequivocally that the condition, even at its most severe stages, can be reversed," explains Dr. Eubanks. "We weren't the first to show improvement could be attained – groups in Scotland had shown some positive outcomes before, but we were the first to show that the problems associated with several neural systems could be rescued. We showed that their epilepsy can be reversed, their thermoregulation can be dramatically improved, and [we showed] that their daily activity patterns can be restored to normal. These are each cardinal features seen in most Rett syndrome patients."
Unfortunately, the genetic model used for these studies was a product of a molecular genetic trickery that doesn't have applicability for humans. However, the crucial thing the experiment shows is that these symptoms of Rett syndrome are reversible, says Dr. Eubanks.
"For a lot of the other conditions that people are trying to cure, you actually don't know that they can be cured," he says. "You think they can, but there isn't any clear, concrete evidence that it can go from terrible to quite good. Here we have that evidence. We know it can happen; we just have to find a way that's clinically relevant."
Drug therapy is one potential curative method and gene editing is another. Dr. Eubanks notes that gene editing could possibly provide a more permanent fix (and it is an area his team is investigating), "but a drug is something that, in theory, could come quicker than genetic corrections," he says. Though a drug wouldn't permanently change the mutated MECP2 gene in Rett syndrome (patients would need to take it for life), a drug could reverse, even eliminate, the disorder's debilitating neurological symptoms, from seizures to motor difficulties to breathing regulation.
There are many different types of genetic mutations in girls with Rett syndrome, but Dr. Eubanks' current drug study is focusing on one particular type – "nonsense" mutations – which account for about one-third of all Rett syndrome cases. In nonsense mutations, a "termination code" is erroneously introduced into the MECP2 gene, which prevents the cell's machinery from making a functional protein. Without those critical proteins, the brain is unable to develop normally, and this results in Rett syndrome's many neurological abnormalities.
"These mutations put an errant stop sign where it shouldn't be," explains Dr. Eubanks. "But there are drugs that can help the cell's system say, 'This is a stop sign that doesn't belong; go past it.'"
In other words, the team is looking for a drug that will stimulate the cell to "read through" the mutation and reach the end of the normal protein coding sequence, so the correct proteins will be made. "By making a drug that will allow the read-through to proceed, we can actually make a functional protein, and allow the brain to regain proper function" he says.
A drug to remove
a genetic 'stop sign'
Dr. Eubanks' research team is in the lab, looking at individual cells magnified hundreds of times. Dr. Eubanks points to a normal cell and then to an MECP2-deficient "mutant" cell.
The team has engineered the MECP2 protein so that when it binds to beacon sites in normal cells, you can see bright fluorescent dots that indicate a properly functioning protein. In the mutated cell, these green dots are absent. If the mutant cells are corrected, the bright fluorescence dots reappear. "We're trying to fix the molecular deficits of the mutant, so this is one of the ways we can see directly if it works," says Dr. Eubanks. "We will only see the fluorescence if the drug worked, and we make the correct protein."
In partnership with a medicinal chemist based in Chicago, Dr. Eubanks says they are testing both novel compounds and already-existing drugs that are used to treat other ailments.
"It's still got a few stages before we get into the clinical trials, but ultimately that's where we want to go," says Dr. Eubanks.