Terry and Georgia Pirovolakis were desperate to learn what was wrong with their baby boy.
The answer would leave them devastated.
In 2019, after repeatedly inconclusive tests, two-year-old Michael was diagnosed with an ultra-rare, neurodegenerative illness known as SPG50.
Michael would be quadriplegic by his 20th birthday, his doctor said — if he lived that long.
In the wake of the news, the life the couple had imagined for their son seemed to shatter around them, they say.
“Literally everything we had hoped for for Michael was pretty much taken away from us,” says Georgia. “There was no high school, there was no university. There was no getting married, having kids, no first love, no graduation. All the things a parent wishes for their child, it’s kind of vanished.”
Yet even in the depths of their grief, Terry says, the path before them was crystal clear — to do whatever they could to make Michael better, no matter the cost.
“We had no choice,” he says. “Doing nothing was impossible.”
The following months saw the couple connect with leading scientists, liquidate their life savings and throw themselves into fundraising for a cure.
Then, years and $4.5 million later, researchers made a breakthrough.
Something’s wrong with Michael
Michael was born in December 2017 in a “normal, healthy birth,” Terry says. “We were home within three hours. Everything seemed fine; we were going on with our lives.”
He appeared a normal, albeit quiet, baby. Michael was calm where his two older siblings had been rambunctious. “He just sat around and watched the commotion happen around him,” Georgia recalls.
But as the months rolled by, his mom grew anxious. Michael started missing developmental milestones his brother and sister, Zach and Zoe, had flown past. By the age when Zach had been self-feeding, “Michael wasn’t even lifting his hands,” she says.
Doctors took Michael through a battery of tests, but none delivered answers. “With every test that came back negative, it was like a sigh of relief,” Georgia says.
“But at the same time, we were like, ‘Well, what’s wrong with him?’”
‘It was the worst thing that could ever happen to us’
It wouldn’t be until two years later, in April 2019, that the couple would learn from a genetic test the extent of Michael’s condition.
“They told us he’ll have developmental delays. He’ll never walk, he’ll never talk,” Terry says, recalling the doctor’s advice to their family: “Go home and give him the best life you could. But don’t expect too much from Michael, because this disease is devastating.”
“We went home that night and I died,” Terry recalls. “I just cried in the street for a few hours.”
“His future was so bleak,” Georgia says, through tears. “So we were like, ‘At least we have to try to make it a little better.’”
What is SPG50?
There is, essentially, a typo in Michael’s DNA.
A random mutation rendered just one of his nearly 20,000 protein-producing genes useless. The gene, named AP4M1, plays a key role in a person’s development; without it, Michael’s brain, muscles and nerves would begin to deteriorate.
“It is a relentlessly progressive disease. And the ultimate prognosis is quite dire,” says Dr. Jim Dowling, the clinician who helped first diagnose Michael.
“By the second decade of life, pretty much everybody with SPG50 will not be able to use their legs meaningfully and will have lost most use of their arm function as well,” says Dowling, a senior scientist at Toronto’s Hospital for Sick Children.
It results in moderate to severe intellectual disability, as well as “seizures and movement disorders, which become more and more burdensome as the disease progresses.”
Dowling suspects fewer than 100 people around the globe have been diagnosed with the condition. Most will die by the time they reach adulthood.
Grasping at straws
Michael was immediately enrolled into therapy programs, but his condition kept getting worse. Three months after his diagnosis, Michael suffered his first major seizure — spasming for two hours while his parents watched helplessly. “It was the scariest thing I ever experienced,” Terry says.
His parents kept pressing forward. While Georgia took care of their kids at home, Terry searched for anyone who could help. When he wasn’t working his day job as an IT director at CIBC, Terry was attending medical conferences, connecting with parents placed in similar situations and “bugging” top experts and companies.
After months of searching, one of those contacts finally offered the prospect of help.
Terry had flown out to a conference in Washington in search of Steven Gray, a leading molecular biologist at UT Southwestern Medical Center.
The pediatric expert didn’t mince words: Michael’s condition could likely be remedied with gene therapy — but, because SPG50 was so rare, no one was interested in funding a treatment.
The years-long process of creating, testing and taking a drug to clinical trials would cost no less than $3 million, he told Terry.
Companies are reluctant to put funding toward rare diseases, which offer little prospect of a return on the investment, Dowling explains.
Even when researchers know a treatment is possible, they’re rarely provided the resources to actually produce it: “There are many, many conditions like SPG50 that could benefit from gene therapy,” he says. “The hurdle relates to cost.”
Racing to fund a cure
“As soon as we found out that something could be potentially done, I basically said to (Georgia), I’m gonna make Michael better,” Terry says. “But you have to keep our family together.”
The couple hired Gray and his colleague, Xin Chen, and immediately got to work fundraising for and co-ordinating parts of the research effort.
They liquidated their life savings and sold all they didn’t need — but that didn’t come close to the money required. So the couple opened a GoFundMe account, founded a registered charity named the CureSPG50 Foundation and organized grassroots fundraising drives, such as “galas and golf tournaments and lemonade stands and barbecues.”
The couple knew the commitment would weigh on their family and other two children. But Terry says they felt there was no other choice: “I would have sold my soul to save my child.”
For the next three years, Terry worked his day job from 9 a.m. to 5 p.m. to provide for his family. “From five until nine, I was a parent,” he says. “And from nine until two in the morning, I was a parent scientist.”
Meanwhile, Georgia was their rock. Michael “literally had therapy every day at that point, he had speech therapy, physiotherapy, you name it,” she explains. “And then I had another two children I had to balance, and they needed some sense of normal.”
Georgia had to quit her job in project management. “There was no way I could work anymore,” she said. “That was a whole other chapter of my life that I had to let go of.”
“It was rough. But they all needed their mom.”
As word about their plight spread, the family’s community united behind them. “Our community in East York came together and did, like, 90 per cent of these (fundraising events) without me even involved,” Terry says.
Tammy Dewhirst, whose children went to the same school as Zach and Zoe, remembers feeling “compelled” to do more than just donate when she learned about Michael. She was among the first to organize a fundraiser for their cause, setting up a charity concert that ended up raising more than $25,000.
“This is a pretty close-knit community. … Everybody knows Terry in this neighbourhood,” she says. “To get a diagnosis like that with your child, and then to become such leaders, not only for Michael, but other children in that spectrum of really rare diseases — I think they are heroes, honestly.”
The momentum only snowballed from there. By 2023, the family had raised a total $4.5 million.
The discovery
While the Pirovolakis family drummed up funds, a multinational group of scientists raced to create and test a treatment from scratch.
Research began in Gray’s lab, with the project assigned to Chen, an assistant professor of pediatrics at UT Southwestern Medical Center.
“We immediately start this project,” Chen says.
Their plan was deceptively simple. Michael had a faulty AP4M1 gene, so, if they gave his cells a working copy, his symptoms should get better, Chen explains.
The tricky part was getting the new gene inside and working in human cells. For this, the researchers used a modified virus capable of injecting engineered DNA inside cells without damaging its target’s genome, according to the team’s paper, recently published in Nature Medicine.
“It cost half a million to make the gene therapy and prove it. It cost us a million to do safety studies,” Terry explains. “It cost us $2.5 million to make the drug — and then it costs another million to dose three kids.”
To save time, many of the required experiments and steps, from creating the genetic construct to engineering mouse models, were done at the same time. “Before we even went to Health Canada, we started our (toxicology) study, and before we even got those results back, we had our clinical batch made,” Terry says.
“That’s how we did it in only three years. If we would have done everything in series, it would have taken five-plus years.”
Gray says his lab has worked on more than two dozen different diseases, most of which received similar funding from patient advocacy non-profits like the CureSPG50 Foundation. Chen says the money raised by CureSPG50 “speeded up our scientific research without any hesitation like a laserlike focus.”
“A lot of things came together, it is actually incredible,” he says. “Because our previous work … it took us about eight years to get to clinical trials.”
The day of the operation
The team’s SPG50 treatment was submitted to Health Canada in November 2021 — and in a “remarkably quick” turnaround time, the promising medication got the greenlight to start clinical trials just one month later, days after Michael’s fourth birthday.
SickKids had already agreed to do the in-clinic treatments before the drug was made, Terry says, and Michael was to be its very first human recipient.
The operation, scheduled for March 2022, would be performed by Dowling — a “full circle moment” for the clinician who helped first diagnose Michael.
The “nerve-wracking” procedure involved injecting several million gene therapy particles directly into Michael’s spinal fluid, Dowling explains. The pressure felt crushing — and not just because he held the product of years and millions of dollars in his hand.
“This is a drug that had never been given to a human before … the medicine isn’t reversible, there’s no way to stop any impact of the gene therapy, positive or negative,” he explains. “It’s clear that gene therapy is not without risk. So we were very, very cautiously observing him” after the procedure.
Michael’s parents and a team at SickKids anxiously monitored his progress for the next 12 months. Even with the treatment, Dowling and his team expected to see some signs of the disease worsening in the toddler — but it didn’t.
Instead, his condition stabilized and, gradually, it began to improve.
One month after the operation, the four-year-old was able to stand with his heels on the ground for the first time, while before his feet were locked in an arched position, Terry says.
Then came something no one expected.
Michael’s behaviour started to change. He began hugging and kissing his parents, Terry says, showing signs that “he knows what affection is.”
And, while still non-verbal, Michael made significant progress in his communication, pointing out “what he wants to eat, what he wants to wear.”
Even then, his parents refused to celebrate: “I’ll be honest, I was just like, ‘Let’s wait and see,’” Georgia says. “It’s very hard to celebrate with something so unknown. You’re always holding your breath, and hoping for the best.”
The aftermath
Today, Michael is doing better, Georgia says. He’s still non-verbal, but has learned to communicate with a device and his body language.
“He has a great support system, he had a great school that he attended where they really celebrated his achievements,” although he’ll be headed for a different school next year.
Michael loves going for swims at the beach with his parents and two siblings. “He really loves hanging out with other children, he loves a lot of the typical things that other kids his age do,” Georgia says. “But at the same time, I could tell he gets frustrated because he wants more independence.”
Terry isn’t done yet. His experiences have led him to his “one goal in life,” he says — to help deal with rare diseases in young children, starting with SPG50.
“I tried to give the drug away after Michael was treated, but no one wanted it, because it’s so rare,” he says. He decided to do it himself instead, founding a company called Elpida Therapeutics to push the treatment and others like it through clinical trials. He quit his “very successful” job in May to work on the therapeutics full-time.
Elpida had just dosed its seventh SPG50 patient in Spain on Wednesday, and plans to treat 20 more people this year if it can raise the funds.
Their GoFundMe and charity, CureSPG50, is still accepting donations to fund more doses of Michael’s treatment.
Meanwhile, after securing millions in grants and philanthropy, his company plans to tackle another devastating, rare genetic illness: Charcot Marie Tooth disease type 4J.
All the while, Terry and Georgia are keeping vigilant of any sign of SPG50’s return in their son.
“He’s not where I want him to be — I want him to be normal, any parent of a disabled child would want their child to be normal,” he said. “He was never going to be that child we prayed he would be one day.
“But hopefully we gave him a better life, so that when me and Georgia are gone from this planet, he can tell someone ‘I’m hungry.’”
