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Single-patient gene therapy clinical trial at SickKids carves a path for Precision Child Health
8 minute read

Single-patient gene therapy clinical trial at SickKids carves a path for Precision Child Health


A SickKids team of doctors and researchers conducted a gene therapy clinical trial for a child with SPG50, one of the first examples of individualized genetic medicine.

Young child sits on adult's lap. Adult is wearing a hair net. Another adult stands behind them.

Meet Michael Pirovolakis, age 4, and his parents Terry and Georgia.

Michael was one year old in 2019 when he underwent genome-wide sequencing at SickKids, which revealed he had two disease-causing variants in a gene called AP4M1.

TORONTO – A team at The Hospital for Sick Children (SickKids) has delivered an individualized gene therapy in a single-patient clinical trial for four-year-old Michael Pirovolakis, with the aim of treating Michael’s ultra-rare genetic condition, spastic paraplegia type 50 (SPG50).

Michael was one year old in 2019 when he underwent genome-wide sequencing at SickKids, which revealed he had two disease-causing variants in a gene called AP4M1. These variants result in SPG50, a progressive neurodegenerative disorder that causes developmental delays, speech impairment, seizures, a progressive paralysis of all four limbs, and can be fatal. In the years following his diagnosis, Michael experienced persistent developmental delays and progressive, increased muscle spasticity.

At the time of his diagnosis and to this day, Michael is the only known patient with SPG50 in Canada.

It’s believed there are approximately 80 children around the world with SPG50, making the condition an “ultra-rare disease.”

“We often think of rare disease as something that impacts a very small number of patients. In reality, it’s estimated that more than one million Canadians have a rare disease and one in 25 children in Canada will be born with some type of a rare disease,” says Dr. Jim Dowling, Staff Physician in the Division of Neurology and Senior Scientist in the Genetics & Genome Biology program at SickKids, who led Michael’s clinical trial.

Man wearing yellow scrubs, surgical mask, hairnet and glasses. He holds a box and stands in a room filled with hospital equipment.

“While an individual disease may only be seen in a few patients, rare diseases as a group of conditions are anything but ‘rare.’ There is a significant unmet need to develop and translate innovative treatments from the bench to the bedside for patients with rare diseases like SPG50.”

- Dr. Jim Dowling


Michael’s treatment options were extremely limited and his parents, Georgia and Terry, started the charity, CureSPG50, raising millions of dollars in the hopes of developing a gene therapy that could help Michael and others like him with SPG50. They worked with doctors and companies in the U.S. and Canada to coordinate the research, development and manufacturing of a gene replacement therapy that is meant to provide a normal version of the AP4M1 gene.

“When Michael was diagnosed, we knew we would do anything, go anywhere and give up everything to save him,” says Terry, Michael’s father. “As they say, it takes a village and our village showed up. Thanks to our incredible community of donors and the tireless work of physicians, scientists and researchers across the world, we were able to create a first-ever gene therapy for SPG50.”

Child sits in a wheelchair holding a tablet. Three adults in medical gowns, caps and masks are present. One leans over and speaks to the child.

Erica O’Keefe, Nurse at SickKids, checks Michael before his treatment.

Once the therapy had been successfully tested in animal models in the lab and was ready to be given to Michael, a team of SickKids doctors and researchers sprang into action to open a clinical trial. Clinical trials are a crucial part of the drug development pipeline and are often the point at which potential therapeutics will fail.

SickKids had never before conducted a gene therapy clinical trial for only one patient. Dowling led the design of the trial, which was key to ensuring Michael’s safety and the integrity of the data being collected on the therapy. The clinical research team consulted with experts around the world and coordinated multiple teams and services within SickKids to be able to provide such a novel treatment. SickKids received Health Canada approval for the trial, and only three years after Michael’s diagnosis, in March 2022, he received a therapy designed specifically for his unique condition.

Three people stand together reviewing a document. They wear hospital masks and eye protection.

Drs. Manohar Shroff, Radiologist-in-Chief, Farrukh Munshey, Anaesthesiologist and Dowling, discuss Michael’s treatment.

“Successfully conducting the trial for Michael was not only a key milestone for him and his family but also for achieving SickKids’ vision for Precision Child Health, a movement to deliver individualized care for every patient,” says Dr. David Malkin, Co-Lead, Precision Child Health, Director of the Cancer Genetics Program and the CIBC Children’s Foundation Chair in Child Health Research at SickKids. “Not only can rare diseases be a springboard to figure out how to treat more common conditions, but learnings from Michael’s trial will help carve out a path for SickKids to explore innovative, precision-based treatment options for other patients with rare, genetic diseases.”

More than three months later, Michael is doing well and there are some indications his symptoms may be improving. He will be monitored over time to see whether the therapy effectively slows the progression of his disease and potentially reverses some of its impacts. CureSPG50 is working with institutions around the world to establish clinical trials for other children with SPG50 and continue testing the new therapy.

What is Precision Child Health?

Watch a quick video to learn about our vision for health care that is individualized to each patient’s unique characteristics.

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