Michael Pirovolakis’s huge smile was visible behind his pacifier as he pushed his little red walker down the hallway with all his might. His father, Terry, cheered him on as his mother, Georgia, extended her arms, willing him to take just a few more steps. It isn’t easy for the 19-month-old to walk, but like most toddlers, he’s determined to do it.
“Michael is a happy little guy who works really hard to do basic things that kids do naturally, but he never gives up,” his mother, Georgia Kumaritakis, told Al Jazeera. “He keeps going and he tries with all his will to do simple tasks like crawling and walking and feeding himself.”
When Michael was born a few days before Christmas in 2017, his family marveled at his big blue eyes and long, soft eyelashes. His brother and sister jockeyed to cuddle him in the hospital room, and his parents took for granted that he would grow up just like them. But when Michael was six months old, his parents noticed he didn’t reach for things with his hands. They grew concerned about his health, and took him to the paediatrician.
At first, Michael was diagnosed with low muscle tone and microcephaly. But after an MRI revealed anomalies in his brain, he underwent genetic testing and was diagnosed with spastic paraplegia 50 (SPG50), an ultrarare neurodegenerative disease. The ride home from the doctor’s office to the family’s home in Toronto, Canada that April day was a blur.
“We came home, just curled up into balls and just cried,” Terry Pirovolakis told Al Jazeera. “You couldn’t believe what was going on. I would go to the park and just cry for an hour just to get out of the house.”
SPG50 affects the brain and spinal cord and causes moderate to severe intellectual disability and paralysis, according to the National Organization for Rare Disorders.
The illness is so incredibly rare it is difficult to track; some cases are never diagnosed. Berge Minassian, MD, the division chief of child neurology at UT Southwestern Medical Center in Dallas, Texas in the United States, estimates there are fewer than 100 people with SPG50 in the world. Data compiled by Boston Children’s Hospital puts the number of confirmed cases at 57 as of September 2019. And while there is no cure, an experimental gene therapy could help prevent the illness’s progression.
“Because this disease is caused by a single gene that is missing in Michael, there is the possibility of doing some research whereby one could replace that missing gene in Michael’s brain,” Minassian told Al Jazeera.
Gene replacement therapy for Michael would cost several million dollars. It would not be fully covered by health insurance – a situation that Minassian calls “heartbreaking”.
Michael’s parents say they are up to the challenge of finding a cure for their son. Because his condition is so rare, few governments, private foundations or pharmaceutical companies are interested in funding research, which leaves families to come up with the money on their own.
Pirovolakis and Kumaritakis have read research papers, spoken to families who have used gene therapy, and contacted doctors around the world, including Minassian and his colleague, molecular biologist Steven Gray, PhD. They’ve also thrown themselves into raising money to get a gene-therapy clinical trial up and running for Michael.
“We are fighting for our son’s life, for a normal life,” Kumaritakis said. “But the financial burden is unimaginable for regular people … No one is going to give you $3m and say, ‘Here you go, cure your boy.'”
Minassian and Gray’s research is focused on finding cures for so-called “orphan diseases” – conditions whose rarity makes attracting research dollars virtually impossible.
Gene therapy – the treatment that could save Michael – is a cutting-edge technology that uses a clinical-grade virus to cross the blood-brain barrier and deliver the missing gene to the neurons and other cells.
“We remove the contents of the virus and put the gene in, and the virus becomes like a delivery truck that could deliver the gene,” Minassian explained. “But because the brain has so many cells – it has maybe a 100 billion brain cells – we need the virus to go into all of those brain cells. So we have to produce a very large amount of this virus.”
In addition to carrying high costs, gene therapy is also considered “risky” and is “currently being tested only for diseases that have no other cures,” according to the US National Library of Medicine.
Minassian said gene therapy has already been used successfully to treat spinal muscular atrophy, which is similar to SPG50. But because it involves a one-time dose of the gene-carrying virus, pharmaceutical companies charge millions of dollars for it, “a high price that makes up for all the investment in making it and doing the research,” Minassian said.
The alternative is to have governments or private foundations fund the research.
And while some might not see curing a disorder that affects less than 100 people worldwide as a good investment, Minassian said treating diseases like Michael’s could lead to cures for more common ailments in which multiple genes are involved, such as multiple sclerosis, Alzheimer’s and Parkinson’s.
“To fix those diseases, we need to learn first how to fix the diseases where single genes are defective, such as Michael’s disease,” Minassian said. “Research in these rare, terrible diseases of children is going to be the springboard for us to figure out how to treat the common diseases that afflict every one of us.”
“It’s a societal decision. Do we want to invest in these advanced approaches to help us all be better, or do we want to invest in the war industry and so on?” Minassian asked.
In the absence of such investment, families like Michael’s must ask friends and strangers for help. So far, the GoFundMe page for Michael’s gene therapy has raised more than $499,000 in three months from more than 3,000 donors. The family says they will use any extra funds to support gene therapy for other SPG50 patients.
But finding the money is just a first step. Pirovolakis said his family will then need to provide proof of concept, manufacture a clinical-grade drug, undergo safety studies and request the US Food and Drug Administration’s permission to proceed with a clinical trial.
All the while, Michael’s disease is taking its toll on his body. Michael currently can’t walk on his own, and he does not talk. Spasticity and neurological delays could begin as soon as age three, which is a little more than a year away, his father said. By age 10, Michael is expected to lose the ability to walk. Between the ages of 10 and 15, he will become paralysed from the shoulders down and lose some of his brain function.
“If we could do the $3m today, I would be screaming from rooftops and knocking on doors,” Pirovolakis said. “I’d sell everything that we own – cars, rings, whatever it was to do it. Unfortunately, it’s going to take 18 to 24 months to get this cure.”
The couple currently pays between $3,000 and $5,000 out of pocket per month to supplement Michael’s physical and occupational therapies and other treatments. Seizures frequently send him to the hospital.
As the couple struggles to give their other two children a semblance of a normal life, neighbours have stepped in to help, putting up signs, raising money and throwing on their bathrobes when they see the lights of an ambulance approaching the family’s home in the middle of the night.
“We feel like we have an army behind us,” Pirovolakis said. “Two or three neighbours will be standing there saying, ‘We’ll watch the other kids for you, just go.'”
In addition to their uphill financial battle, Michael’s parents also struggle with the uncertainty of his future. “It’s the unknown,” says Kumaritakis. “When you have a normal child who is born with no health issues, you can kind of see their path – they’ll grow up, they’ll develop, they’ll have a life. But we don’t know what Michael’s future is. We don’t know how far he’ll go.”
This is the first story in AJ Impact’s three-part series on the human faces behind rare diagnoses and the challenges researchers and patients face in funding research and accessing treatment.