Two fathers, both dealt a harsh fate, meet me on a sunny spring day in Carlsberg Byen, Copenhagen, where Nordic Healthcare Group has provided the space.
Seven years ago, when Canadian Terry Pirovolakis from Toronto and Danish Søren Jarl Christensen from Horsens each became fathers to newborn sons – Michael and August – they believed their boys were healthy. But it soon became evident that not everything was as it should be.
Canadian Michael struggled to lift his head and did not develop at the same pace as other children. Danish August looked over people’s heads and was difficult to engage eye contact with. Initially, doctors dismissed these signs, saying not all children develop at the same speed.
As symptoms gradually worsened for both children, doctors spent a long time trying to determine what was wrong. It was only after thorough genetic testing, when Michael and August were one and a half and four years old respectively, that it was discovered they both suffered from the extremely rare disease hereditary spastic paraplegia, abbreviated SPG50 – a condition with approximately 125 cases worldwide.
This neurodegenerative disease results from a defect in the AP4M1 gene, preventing the central nervous system – brain and spinal cord – from producing a vital protein. Consequently, the children’s nervous systems will progressively deteriorate.
First, they lose the ability to use their legs, confining them to a wheelchair for life. Later, they lose the use of their hands. The disease also affects cognitive abilities, which, according to Søren Jarl Christensen, means his seven-year-old son August has no speech and possesses cognitive abilities comparable to a one- or two-year-old child.
The disease also brings spasms and epileptic seizures. The prognosis is bleak, and most do not survive past their teenage years or early twenties.
Desperation sparked hope
Terry Pirovolakis, an IT specialist, will never forget the day his son was diagnosed. On April 2, 2019, he and his wife were told there was no treatment for the extremely rare disease, and they should go home and cherish the time they had left with their child.
»We were devastated, and I broke down crying on the floor once we got home. The news that there was no treatment for my son ignited an inexplicable anger in me, despite being a fundamentally calm person«, says Terry Pirovolakis, who becomes emotional and teary-eyed just talking about it.
But the desperation also sparked hope in Terry Pirovolakis.
»I shut myself in a closet and Googled for 20 hours straight. That led me to realize that gene therapy might be the salvation for our son«.
Just a month after his son was diagnosed, Terry Pirovolakis attended the largest scientific conference on gene therapy in Washington, D.C., where he put up a poster that read: ‘Wanted: A cure for Michael’.
At the conference, he met seven of the world’s leading gene therapy experts and representatives from the FDA and NIH.
»I asked all of them what they would do if Michael were their son. Nine out of ten said gene therapy. When I asked who should develop the gene therapy, nine out of ten said Dr. Stephen Gray from UT Southwestern Medical Center in Dallas, Texas. When I approached Stephen Gray, he said he was too busy. So I said I wouldn’t accept that and that I would pay him to do it. Then he said: Let’s do it«, says Terry Pirovolakis.
A team of world-leading experts was assembled and began developing a gene therapy for Michael. Parallel to this, Terry Pirovolakis managed to raise a total of 20 million kroner thorugh a work frenzy.
»We refinanced our house, sold all our stocks, and I contacted the government to start the charity CureSPG50, where the collected funds would go towards developing a treatment«, says Terry Pirovolakis.
The mission succeeded in under three years. First, a harmless virus was equipped with a healthy version of the gene the children were missing. After successfully testing the gene therapy on mice, rats, and monkeys, it was time to test it on the first patient – Terry Pirovolakis’ own son, Michael.
On March 24, 2022, the virus with the healthy gene was injected into his spinal fluid, giving it access to his brain, where the virus could transport the healthy gene into the nerve cells it infected. This allowed the nerve cells to produce the vital protein Michael’s brain lacked.
The one-time treatment appears to be effective, Terry Pirovolakis says.
»The gene therapy has halted the spread of the disease. Since Michael received the treatment, he hasn’t fallen or had seizures. He can now stand with his heels on the ground and walk further with the help of a walker. Brain scans show that the brain atrophy in Michael’s brain has stopped«, says Terry Pirovolakis and continues.
»Michael is a happy and lovable boy. He was so severely affected by the disease before the gene therapy that he will never be completely healthy or walk unaided. But I pray that he will one day be able to speak«.
Determined to save other children
The achievement is so significant that one of the world’s leading journals, Nature Medicine, chose to publish the news of the treatment, with Terry Pirovolakis listed as an author. This does not make the Canadian father take his foot off the gas. His mission is even greater.
»My plan is for all children worldwide with SPG50 to have the opportunity to be treated with gene therapy, and my hope is that the same treatment principle will be used in the future to treat other rare diseases in children, where large pharmaceutical companies won’t invest resources due to the small financial return«, says Terry Pirovolakis.
This is also why Terry Pirovolakis is in Copenhagen today with Søren Jarl Christensen. He wants to do everything he can to ensure August receives the same treatment as his son.
In fact, everything was planned and ready for August and another Danish boy to receive the treatment in the U.S., where the medication would be provided for free. But that plan fell through when President Donald Trump came to power, as the new administration significantly cut NIH budgets, affecting funding for experimental treatments. Thus, the two Danish boys missed the opportunity for treatment in the U.S.
Today, there are two doses of gene therapy in a freezer in San Sebastian, Spain, potentially able to halt the disease in the two Danish boys. The two doses cost 4.8 million kroner, and Søren Jarl Christensen founded the association ‘Sammen for August’ (Together for August) to raise funds for the treatment of Danish patients with SPG50. So far, he has managed to collect 1.5 million kroner.
»In our fight to find a treatment for my son, I discovered through an American network that there were four other Danish children with the rare disease, which inspired me to start the association. As it stands now, two children including our August, have agreed to receive the experimental treatment if we can raise enough funds«, says Søren Jarl Christensen.
Rigshospitalet has agreed
August’s father has been fighting for a year to find a hospital in Denmark to administer the treatment. With support from Terry Pirovolakis, he has succeeded, and Rigshospitalet will administer the treatment to the two boys once they receive approval from the scientific ethics committee, the Danish Medicines Agency, and the Danish Working Environment Authority to start the experimental treatment. It is expected that the treatment can begin in early autumn.
Alfred Peter Born, chief physician in pediatric neurology at Rigshospitalet, with experience in gene therapy, will lead the treatment of Danish children with SPG50. They agreed to provide the treatment as long as it benefits all patients with the diagnosis and is not earmarked for specific individuals.
»Since this is an advanced treatment with a gene therapy not yet approved by health authorities, and only a few children have been treated worldwide, we will conduct the gene therapy as part of a scientific study, where we will collect data and contribute to greater knowledge about this treatment«, says Alfred Peter Born.
The chief physician is impressed by the fact that Terry Pirovolakis’ initiative to develop a gene therapy for the extremely rare disease has succeeded.
»It is fascinating that a father of a sick child can have such a drive and gather skilled researchers and doctors to develop a gene therapy from scratch. It is truly quality work, and that is why we have agreed to try the gene therapy in a Danish context«, says Alfred Peter Born.
Alfred Peter Born and his colleagues at Rigshospitalet already have experience treating children with rare diseases using gene therapy. This includes spinal muscular atrophy, a hereditary form of muscle wasting caused by the child inheriting a defective version of the SMN1 gene from both parents.
’We have had positive results using gene therapy to treat that disease. What’s remarkable is that it only requires a single treatment. Our experience indicates that if we treat patients early, before symptoms appear, there is a strong likelihood they will stay healthy and develop normally or nearly normally,’ says Alfred Peter Born.
He hopes the gene therapy for SPG50 will have the same effect on children, with the best results likely achieved by starting treatment early. The therapy cannot repair existing damage, but the hope is it can halt the disease’s progression.
»If the gene therapy stops the breakdown of brain nerve cells, we can hope that the nerve cells in the young brain will have the peace to develop normally and give the patient the ability to acquire new skills. Therefore, it is crucial to administer gene therapy to children who still have significant developmental potential in their brains«, says Alfred Peter Born.
Affected families must pay
Typically, large pharmaceutical companies finance scientific trials at hospitals in their quest to get new medications approved. Therefore, it is unusual for a nonprofit organization to offer a self-developed medication at no cost for an extremely rare disease with no existing treatment.
The chief physician calls it an exciting development, as it could pave the way for treatments for extremely rare diseases.
»There are many rare childhood diseases where no commercial entities are involved. I think we will see more associations or individuals in the future raising funds and paying someone to develop a treatment. This could become a model for organizing drug development for rare diseases«, says Alfred Peter Born.
Since the gene therapy for SPG50 is not approved and must be administered as part of a scientific trial, Rigshospitalet does not have the budget to cover hospital expenses according to Alfred Peter Born. If the hospital had to cover the costs of the trial treatment, it would impact other patient care at the hospital.
This means the association ‘Together for August’ – in addition to the medication costs – must also cover the hospital expenses Rigshospitalet incurs during treatment, estimated at 1.75 million kroner. August’s father is frustrated that they must also cover hospital costs.
»We know that for children with SPG50 in Germany, Italy, England, and Spain who have received gene therapy, the state covered hospital expenses and often the medication costs as well. As a Danish taxpayer, I think the same should apply in a wealthy country like Denmark, and that it shouldn’t be the individual family with a very sick child covering the costs«, says Søren Jarl Christensen.
He continues:
»One should also consider that if the gene therapy halts August’s disease and releases his mind because his cognition improves, the public expenses for his daily care would also decrease. So, the investment in the gene therapy could end up being economically beneficial for society while improving the treated children’s quality of life«.
Politiken reached out to Danish Regions (an organisation representing all Danish regions) and the Capital Region of Denmark (responsible for administration of the hospitals in the region) for a comment, but they have not responded.
As we step back out in the spring sunshine, the two fathers stand shoulder to shoulder. Søren Jarl Christensen takes out his phone and shows two videos of August. In one, he elegantly maneuvers his wheelchair on a dance floor to music played by an orchestra during a vacation in the U.S. He smiles. In the other, he trains on a special treadmill at the physiotherapy department of Skejby Hospital.
»What characterizes children with SPG50 is that they are in an incredibly good mood. They are almost always happy and cheerful. August is just a super happy boy and a bit of a prankster«, says Søren Jarl Christensen.
He also shares that August has a fantastic relationship with his older sister, Sara, who is a year older than him.
»Naturally, when Sara is met with a smile from August and a teasing glance, she wants to reciprocate«, says Søren Jarl Christensen.
The older sister has started raising money for her little brother by painting stones and selling them along the road.
»She raised a couple of hundred kroner the first time she did it«, says the father, beaming with a big smile.
Søren Jarl Christensen has gone part-time in his job as a commercial pilot while fighting to fund the treatment for Danish children with the rare disease. But there is also another reason.
»As it stands right now, I only have August on loan. So, I want to spend all the time I can with him until he is no longer here«, says Søren Jarl Christensen, receiving a supportive pat on the shoulder from Terry Pirovolakis.
A moment later, the two fathers walk side by side out of Carlsberg Byen. Søren Jarl Christensen leads the way.
Documentation
AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient
