A gene therapy made specially for a Toronto boy with an ultrarare genetic disorder is safe and appears to have halted the progression of his disease, according to a new paper outlining the results of a single-patient clinical trial that his family raised millions of dollars to fund.

When Michael Pirovolakis, now 6, was diagnosed with spastic paraplegia type 50 (SPG50) at 16 months of age, he was the only patient in Canada known to have the disorder.

His prognosis was grim. Doctors told his parents, Terry Pirovolakis and Georgia Kumaritakis, that Michael’s progressive neurodegenerative disorder would cause intellectual and development delays, prevent him from talking, and eventually rob him of the ability to walk.

Rather than accept Michael’s fate, the couple upended their lives in search of a treatment for SPG50, raising $4.5-million and working with scientists at the University of Texas Southwestern Medical Center in Dallas to create a bespoke gene therapy for their son.

In March of 2022, Michael received the experimental therapy through a one-time injection in his spine at Toronto’s Hospital for Sick Children as part of a Phase 1 clinical trial in which he was the only participant – a first for SickKids.

The results of that trial were published Friday in the journal Nature Medicine.

“It almost seems fantastical what was able to be accomplished,” said Jim Dowling, a neurologist and senior scientist in the genetics and genome biology program at SickKids.

Typically, Dr. Dowling said, parents who devote themselves to finding a cure or treatment for a rare disease do so for the next generation, knowing that any breakthroughs they spur will come too late for their own children. The fact that Michael – “the inspirational patient,” as Dr. Dowling called him – was able to benefit, “is incredibly exciting.”

The degree of benefit is clear to Michael’s parents, and is described in the paper, but so is the reality that fixing Michael’s underlying genetic defect can’t undo the damage done to his brain before he was treated.

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His cognitive scores improved in the first year after gene therapy, as did his fine and gross motor skills, according to scales used to measure child development.

Crucially, he hasn’t declined physically, as would be expected of a child with SPG50. He’s now able to stand with his heels on the ground, unlike children with spastic muscle conditions that force them onto their tippy toes. But Michael still can’t speak.

One of the challenges of evaluating the efficacy of SPG50 gene therapy in a single-patient trial is that there is no control group to serve as a measuring stick. Untreated children with SPG50 deteriorate at different rates and relatively few have been studied, Dr. Dowling added.

Dr. Dowling diagnosed Michael with SPG50 and is the lead author of the new paper. The second author is Mr. Pirovolakis, Michael’s father, who quit his job in finance to start the CureSPG50 Foundation and a non-profit pharmaceutical company dedicated to developing drugs for diseases too rare to attract research investment from traditional drug companies.

Gene therapy offers tremendous hope to patients with rare genetic conditions, Mr. Pirovolakis said, particularly if newborn screening is expanded so that patients like Michael can be diagnosed and treated before their disease inflicts irreversible damage.

A total of five children, including Michael, have received the SPG50 gene therapy with the help of money raised through the CureSPG50 Foundation, which continues to collect money through a GoFundMe drive. Mr. Pirovolakis said the hope is to provide the treatment to another 18 children in the U.S. and Europe this year.

“What we are seeing, not just in Michael, but in all the children, is cognition improvements,” Mr. Pirovolakis said. Michael has a device on his iPad that allows him to show his parents and older brother and sister what foods he wants, what he wants to wear and what shows he wants to watch. He’s deeply affectionate and loves playing with his trucks, his father said.

“Is he tracking differently than a child that had this disease if he didn’t have the gene therapy?” Mr. Pirovolakis asked. “We just don’t know, but that’s what we’re trying to answer – that, and give Michael a life that would be better than him being quadriplegic and non-verbal when we’re gone from this earth.”