On Saturday, 29-year-old Ryan Dant will walk across the stage in his cap and gown as he graduates from his dream school, the University of Louisville.
It’s remarkable because Ryan wasn’t expected to attend college, let alone the school whose logo he wore on T-shirts and basketball jerseys as a toddler. Because underneath that cap and gown, medications are circulating through his entire body to make this moment possible. Because his parents never gave up, even when they heard there was no chance.
It’s remarkable because Ryan is still alive, despite being born with a death sentence in his genes.
The normal beginnings of rare disease
His father, Mark Dant, likes to say that Ryan was born with a love for baseball. The night before his birth, his parents went to a Texas Rangers game.
The healthy, beautiful boy was born in 1988, weighing 8 pounds, 13 ounces. He was perfect, Mark said. At the age of 3, he could throw a baseball so hard that his mom, Jeanne, made a “no ball in the house” rule. Every night, Ryan would watch baseball games with his family on TV, cheering on Rangers pitcher Nolan Ryan. He loved the fact that he could see his own name on the back of the baseball player’s jersey.
Before enrolling him in day care at age 3, Jeanne took Ryan to the pediatrician. What was supposed to be a routine checkup revealed that Ryan’s liver and spleen were too large, and the Dants were referred to a geneticist. Mark, who had just made lieutenant at the police department in Carrollton, Texas, didn’t believe anything was wrong with his son. He didn’t go with them to see the geneticist. But two weeks later, tests confirmed the diagnosis.
The geneticist said Ryan had a rare genetic disorder called mucopolysaccharidosis I, or MPS I, with a wide-range of symptoms affecting multiple systems in the body. The mutation forms in a gene that makes an enzyme that helps break down byproducts of chemical reactions in cells. The enzyme can’t be produced, leading to a buildup of this byproduct that can cause damage to cells, tissues and organs.
It explained why his spleen and liver were enlarged; the buildup made them 2½ times larger than normal.
The geneticist told the Dants that Ryan would die by the time was 10 or 12. Over time, they would see him change. He would be in a lot of pain, possibly go blind and deaf, suffer a stiffening and curling of the muscles in his limbs that would put him a wheelchair. He would decline mentally.
Soon, he would lose the ability to play baseball.
Mark Dant pressed the doctor, asking about research or medications.
” ‘You have to understand, your son has a disease that is so rare that there aren’t many scientists working on it,’ ” he recalls the doctor saying. “He was telling us to take him home and love him, because he wouldn’t be around long.”
MPS I affects one in 100,000 children globally, according to the National Organization for Rare Diseases.
The Dants immediately decided not to tell Ryan; he was too young to understand. They cried in the hallway before taking him home. That became the new normal for them: crying at night, separately, after Ryan went to sleep. When they weren’t crying, they were watching him sleep, waiting for the inevitable. Mark would wake up on the floor next to Ryan’s bed every day.
“I remember that year being so incredibly painful because we had a happy, playful little boy who was no different than he was before we walked into the examination room, but everything we knew about him was going to change,” Mark said. “And there was nothing we could do about it at all.”
They spent a year in mourning. But the Dants began to wonder whether there was something they could do. Surely, there were other families out there dealing with MPS I.
“I decided after a year to get up off the floor and do something about it,” Mark said.
Tracking down a scientist
Mark started by attending a conference for the National MPS Society. He was shaken and heartbroken to see children in various states of decline. There were no teenagers.
After that, he spent his free time at the library, reading about genetics and the little information available about MPS I. Mark’s research led him to an international symposium in Germany, where a scientist presented on enzyme replacement therapy for another rare disease. He asked the scientist whether it was possible to develop a similar therapy for MPS I.
It’s possible, he was told, but it will take a lot of time and money. Both were in short supply.
All Mark needed to hear was that it was possible. He decided to buy time. After returning home, he researched nonprofits and started the Ryan Foundation. A bake sale in the family’s driveway raised $342.
Through an MPS Society event, Mark connected with another scientist who told him about her brilliant former student at the University of California, Los Angeles. Emil Kakkis was working on an enzyme replacement therapy for MPS I, but struggled due to lack of funding. After meeting Kakkis, Mark knew that he had found the right person.
“He is the most dedicated person because he wants to treat the untreated,” Mark said.
They began a partnership. Donations to the Ryan Foundation would fund Kakkis’ research, hoping to make the therapy a real treatment.
With the support of their community, golf tournaments, corporate donors and philanthropists who learned about the Dant family through news articles, funding began to grow.
‘What will it be like when I die?’
Meanwhile, Ryan was declining. His hands were so stiff that he couldn’t move them. By age 5, he had to bend over to put a shirt on because he couldn’t raise his arms above his head. Mark attached Velcro to his baseball bat and sewed it to his little batting gloves so Ryan could grip it. He struggled to breathe at times.
By age 7, he had to stop playing. Saturday morning baseball games and practices were replaced with physical therapy and doctors appointments. Mark started driving out of his way to avoid going past the baseball field. It caused both of them too much pain.
Severe headaches would cause Ryan to vomit until he passed out. Just thinking about the headaches scared the boy.
Trying to play soccer, he collapsed after rupturing a hernia in his liver. That night, he asked, “Dad, what’s it going to be like when I die?” He asked whether his dog would be with him and where his parents would be. And then he fell asleep.
Mark realized that while they had tried to shield him as much as possible, Ryan knew more than they thought. Other kids at school had heard from their parents that their classmate was in newspaper articles. The stories said he would die, so his classmates said the same thing.
They needed hope more than ever.
Kakkis had been working into the night every night, year after year. He used the funds for researchers and machines. A biotechnology company called BioMarin, formed in 1997, was interested in turning the therapy into a drug called Aldurazyme.
A clinical trial was approved in 1998, and Ryan was invited to be one of 10 children to undergo the therapy in Los Angeles. It was his only chance.
He was scared and didn’t understand why he had to leave his friends to live in another place for months.
“I met Ryan as a very afraid little boy who knew that he was going to have to do these weekly infusions,” said nurse Sarah McNeil, who assisted him during the trial.
After a few weeks of therapy, Ryan couldn’t believe “how little my tummy is.” The enzyme replacement therapy was working, removing years of built-up byproduct in his liver and spleen and returning them to normal size. He continued to respond extremely well to the treatment.
Some of the children had allergic reactions to the infusions, but the trial was expanded over four years. The drug would receive marketing approval from the US Food and Drug Administration in 2003.
Over time, Ryan began to feel normal. His hands uncurled, the headaches went away, and he was able to start playing baseball again. He had lived to see age 12, defying the odds.
“It was a really great feeling to be pack as a part of the team and be able to play a sport that I love so much,” Ryan said. “I could slide back into the normalcy of being a kid again, pick up where I left off, meet my best friend.”
Ryan began to talk about his early childhood dreams for the future again. He wanted to get a driver’s license, go to prom, buy a Mustang and go to the University of Louisville. The weekly four-hour IV drip of Aldurazyme was lengthening his expected lifespan, making all of those dreams into possibilities.
Years of middle school and high school were filled with the perfectly normal things that someone Ryan’s age should be enjoying. He was even able to eventually buy his Mustang.
But another obstacle was just around the bend.
The enemy within
In the latter years of high school, the lights in Ryan’s brain began to turn off. He would study all weekend for an exam, only to have no memory of the information on Monday morning. He was able to graduate, but the problem only grew worse as he moved on to community college.
His annual summer cognitive testing at the University of Minnesota confirmed it: Despite his physical improvement, the mental decline they had always feared was happening, and at a rapid rate.
After years of writing to the equipment manager for the University of Louisville’s football team, Ryan had been told that as soon as he could take a full course load, there was a scholarship waiting for him with the equipment staff. There, he would be able to pursue his dream of working in sports.
But his cognitive decline meant he wouldn’t be able to go to college.
The Dants learned that another clinical trial was happening at UCLA in 2011, one that was testing whether injecting the enzyme into the spinal fluid would help clear byproduct out of the brain. Ryan latched onto the hope of that trial.
But when they tested Ryan by injecting dye into his spinal fluid, it pooled rather than traveling to the brain due to the narrow and clogged pathway of his spine. He didn’t qualify for the trial.
He broke down and sank into a deep depression. A month later, he posted on Facebook, musing about how the journey was never over and full of bumps in the road.
McNeil, the nurse from the first clinical trial, had formed a bond with the Dant family. A friend of Ryan’s on Facebook, she saw the post. She feared the worst and reached out to Ryan and his dad, asking what had happened.
When they told her, it broke her heart. “He’s the only child left still living from the first 10 in the original trial,” McNeil said. “I just thought, ‘He’s made it this far. This just can’t be it.’ ”
McNeil happened to be working with a neuro-oncologist, Dr. Elizabeth Maher, at the O’Donnell Brain Institute at UT Southwestern Medical Center, mostly with brain tumor patients. She told Maher about Ryan’s story and the defeat he felt over his exclusion from the trial.
McNeil raised the question: What if they could use the UCLA trial protocol to get the drug and begin a compassionate use study? Compassionate use is outside of a clinical trial for a medical product that has not been approved, according to the FDA.
“Why wouldn’t we do this?” Maher responded. She recognized that the science was excellent and that it was a potential treatment to help the enzyme cross the blood-brain barrier — protective “Saran wrap for the brain” — which Aldurazyme couldn’t do. But Maher worried about the risk of delivering this enzyme into the spinal fluid and whether it was safe. As they worked through the process to begin the study, the safety question kept Maher up at night.
But Ryan was losing memory retention every day. To him, the benefits outweighed the risk.
In April 2012, the study began. Every 12 weeks, he would go in for a spinal tap that required him to lie on his stomach for 24 hours.
After a month, Ryan felt like his ability to memorize had improved. By three months in, he was reading. After four months, Ryan came running into the clinic to tell Maher that he read a book all the way through over the weekend and remembered it.
The treatment didn’t just stop his cognitive decline. In a groundbreaking development, the infusion reversed it.
“All we hoped for was that we could stabilize it,” Maher said. “We had no expectation at all that he would improve. What this shows is that the right drug that does its specific function, even in the brain, can lead to neuro-cognitive recovery. The damage we thought was being done to the brain was not permanently impairing those circuits. The lights were just turned off. Then, those circuits began to fire really quickly.”
Hope beyond tomorrow
After getting his associate’s degree at Brookhaven College in Texas, Ryan was finally able to attend the University of Louisville and take a full course load. He also began working for the equipment staff.
Cognitive testing showed an increase. His grades improved to As and Bs, and he appeared on the athletic director’s honor roll for the past three years.
This weekend, Ryan graduates with a bachelor’s degree in sports administration. He wants to work in sports management for a professional team.
His hard work ethic has made it possible, and the weekly four-hour IV drips and quarterly spinal injections continue until better science comes along.
Kakkis will be at the graduation. Maher firmly believes that people like him and Mark Dant can change the world. Aldurazyme is now the only approved treatment for MPS I patients. A clinical trial at UCLA, using the treatment that has helped Ryan cognitively, continues. A paper was published this year detailing Ryan’s case study.
“Mark’s desperate search for a treatment for his son has led to insights into neuro-cognitive recovery that was unimaginable,” Maher said.
The Ryan Foundation for Rare Disease Research continues its mission, and Mark is also now the president and CEO of the National MPS Society.
“Some parents don’t really have the desire or drive to do as much work as my parents have,” Ryan said. “It’s amazing to see how hard they’ve worked to improve my life. After being able to walk across the stage and see the journey that I’ve had, now I can see what my next goal is: find a great job, get married, have a family and enjoy life.”
Ryan has always been told what will happen. Now, the gift of not knowing is the greatest one he could have, Mark said.
“For many, many years, I wouldn’t allow myself to visualize Ryan in a cap and gown and enjoying what it might feel like to be a college graduate, because it wasn’t going to happen,” Mark said. “But Ryan, and so many others, made it possible by not giving up.”
This is why Ryan’s graduation isn’t just one of thousands happening across the country this month. He’s one in a million.
By Ashley Strickland