By Shane Perusse
Last summer Russell Viirre, a Ryerson chemistry professor, began testing a new drug that could treat over 4,000 Canadian children living with cystic fibrosis (CF).
Viirre, who is working on the drug along with Christine Bear, a senior scientist at the Hospital for Sick Children (SickKids) is hopeful that their research will increase the life expectancy of patients with CF.
CF is the most common fatal genetic disease affecting children and young adults in Canada.
It mainly affects the respiratory and digestive systems, preventing the absorption of fats and proteins and often leads to infection in the lungs as well as bowel complications.
The daily efforts required to care for a child with CF is a complication that Gillian Maramieri knows well. Her three-year-old son, Matthew, is a “double delta,” which means he shows only the delta-F508 mutation. He has lived with lung and digestive complications his entire life.
In 2009, Matthew had stem cells removed from his stomach after a surgery. These stem cells provided Bear with a pure form of the CF transmembrane conductance regulator (CFTR) protein, which she was later able to synthesize for testing with CFTR-targeting drugs.
The new combination drug that Bear and Viirre are testing, Orkambi, was developed by Vertex Pharmaceuticals. It contains the two drugs ivacaftor and lumacaftor, which work to treat the genetic mutation delta-F508.
The mutation is the result of three missing molecules in the CFTR protein, which is one of the body’s key proteins. It affects 80 per cent of CF patients.
Since 2009, Bear and Viirre have been testing the way that drugs like ivacaftor and lumacaftor interact with the CFTR protein responsible for CF in children and adults.
“(The drugs) are binding to the protein and making it work, which is unusual,” Viirre said. “It’s a lot easier to sabotage a protein but in this case the drugs are causing the protein to behave as they would in a healthy person.”
Orkambi shows potential for treating CF patients, but neither Bear nor Viirre are sure why.
“The question both of our labs are trying to answer is, ‘how are these drugs working?’” Bear said. “We know these drugs are working, but we don’t yet know how or why.
With further study we will be able to make new and better drugs.”
The CFTR protein was discovered at SickKids 25 years ago and has been associated with over 2,000 known mutations related to CF. Although the processes for testing these drugs and their interactions with the CFTR protein are difficult, SickKids is in a unique position to carry out this research.
“There are a lot of CF labs in Canada,” Bear said. “What makes ours unique is that we know how to synthesize a pure CFTR protein for testing.”
Viirre’s main contribution to Bear’s research is the creation of fluorescent molecular tracer probes that highlight where the drugs being tested attach to the complex CFTR protein.
“We’re in a great position to help (Bear’s) work,” Viirre said. “What we’re doing is making these tracer molecules that she can’t buy anywhere else and because we’re right next door it’s very easy for us to collaborate.”
As of today, SickKids is the only lab in Canada researching the CFTR protein with these tracer molecules.
According to Cystic Fibrosis Canada, an estimated one in 3,600 children are born with the condition when both parents are carriers of the mutation. The average person with CF is expected to live to be 40 years old.
The medical complications and preventive measures that allow Matthew to enjoy a normal life can be daunting for both he and his parents.
“He had a perforated bowel before he was born,“ Maramieri said. “Because of that he had a stoma for six months that required surgery and spent six weeks at SickKids.”
Matthew is too young to be given any CF drug treatments yet and must adhere to a daily schedule of preventive measures designed to alleviate the symptoms of his condition.
“Right now, Matthew takes three to four enzymes with every meal,” Maramieri said. “He does mask treatment in the morning and chest physio two to three times a day. On working parents that can be a lot, as well as on a kid that just wants to be a kid.”
Maramieri has Matthew enrolled in several extracurricular activities suggested to her by doctors, such as swimming and gymnastics, and although he has to be watched closely, he is still able to have a normal childhood.
“If he had to be born with CF, I’m glad it was now and not 20 years ago,” Maramieri said. “On a day-to-day basis we try to let him be a child and hope that cure or control is just around the corner.”
For now, Maramieri is hopeful that Bear and Viirre’s research will lead to a drug that increases both the span and quality of life for CF patients like Matthew.