Gene therapy halts progression of rare neurodegenerative disease in Toronto boy

The findings from a single-patient gene therapy trial at The Hospital for Sick Children (SickKids) show promise in halting the progression of a young Toronto boy’s rare disease.

Michael Pirovolakis has spastic paraplegia type 50 (SPG50), an “ultra-rare” neurodegenerative disorder that causes developmental delays, speech impairment, seizures and progressive paralysis. He is believed to be the only child in Canada with the disease.

There are approximately 80 children around the world affected by the genetic condition.

“Michael was diagnosed April 2, 2019,” said Michael’s father, Terry Pirovolakis. “A month later, I was in Washington meeting with all the world experts. Three days later, we had liquidated our life savings. A year and a half after that, we started safety studies. We then made the drug two years in and just under three years, Michael was treated with the gene therapy at SickKids.”

The family raised $4.5 million and worked with scientists in Dallas, Texas to create a gene therapy for Michael in an effort to slow the progression of the condition.

A clinical research team at SickKids administered the gene therapy to Michael in March of 2022.

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“We didn’t know if it was going to kill him or make him better or something in between,” said Pirovolakis.

“It was the scariest day and happiest day because we worked so hard and our community came together to help us make that happen,” he added.

SickKids had never before conducted a gene therapy clinical trial for only one patient.

“The two major outcomes that we monitored in the trial were safety and then effectiveness or efficacy,” said Dr. Jim Dowling, staff physician in the Division of Neurology and Senior Scientist in the Genetics & Genome Biology program at SickKids.

“I think is quite encouraging that the drug is helping to halt the progression of this disease, which is really huge because, the disease progresses ultimately with an inability to use your arms or legs meaningfully and with continued cognitive decline. And so he hasn’t experienced any of those,” said Dowling.

In the 12 months after receiving the treatment, and contrary to the hallmark of neurodegenerative conditions, Michael’s condition does not seem to be progressing further and he has begun to show potential signs of improvement.

“He went from standing on his tippy toes to standing flatfooted … he hugs and kisses my wife, he chooses the clothes he wants to wear, the food he wants to eat,” said Pirovolakis.

Results of the trial have now been published in the journal Nature Medicine.

“This is really one of the first examples of that inspirational individual, Michael, motivating the development of a therapy that actually got back to him. That was something that could help him. I think that offers really amazing hope to the thousands of patients with rare disease who are diagnosed across the country, each year,” said Dowling.

Pirovolakis said he sees hope in gene therapy for patients with rare genetic conditions, like his son.

“I’m getting calls every week by families around the world saying, ‘help me save my child’ … I quit my job, I started a biotech, pharmaceutical company in California. We now have five employees and 20 consultants,” he said.

The family started the CureSPG50 Foundation, which collects funds through a GoFundMe campaign, in hopes of helping other children.

“In a lot of cases you can do something, a therapy can be made, and if you’re an advocate and you work hard enough, you can do what people tell you is impossible. You can create a treatment.”