By Joquita Burka
Photography by Ashley Jones

Tarah O’Sullivan, mother of two children with a rare genetic disease, has returned to school at Clemson determined to help children with rare genetic diseases. And to save her own.

Thursday, October 13, 2016, was a beautiful fall day, made especially perfect for Eric and Tarah O’Sullivan by the birth of their son, Drake. Golden hair, clear blue eyes — the family thought him perfect. And the doctors agreed, clearing him to go home the next day to his eagerly waiting grandparents and siblings. With three children at home aged 3 to 7, the O’Sullivans could enjoy this birth without all that first-time-parents angst. They were seasoned professionals.

That next day, Drake preferred sleeping over eating. But then, that’s common with newborns. Tarah and Eric would wake him for feeding, careful to make sure he got plenty of nourishment.

By Saturday, these experienced parents became uneasy. Drake was just too lethargic. It was harder to wake him for feedings. The O’Sullivans called Drake’s doctor and were assured there was nothing to be concerned about; Drake had been healthy when he left the hospital two days ago. And, the doctors’ office assured them, they would be checking him again on Monday at a scheduled office visit.

But the O’Sullivans’ disquiet grew by the hour. By Sunday evening, Drake would not open his eyes or respond to them. He was growing limp and struggling to breathe. The O’Sullivans rushed Drake to the hospital where the staff flew into emergency mode. Too sick for care at the local hospital, Drake was stabilized for transport to the pediatric intensive care unit (PICU) at Greenville Memorial Hospital. Just 72 hours after birth, Drake lapsed into a coma. And no one knew why.

That unforgettable night was the beginning of a long journey of test after test and a diagnosis by elimination.

Drake continued to decline as each negative test pushed aside another horrible possibility. “You would think that eliminating terrible diseases would be a good thing,” says Eric. “But that just meant we were looking at something very rare.”

Finally, blood tests revealed an ever-elevating level of glycine in Drake’s blood, a symptom of an extremely rare, genetic metabolic disease called nonketotic hyperglycinemia or NKH.

The words “nonketotic hyperglycinemia” meant nothing to Tarah and Eric. But the next words were clear: Drake had a less than 10 percent chance of survival.

The diagnosis was like a starter’s pistol for the O’Sullivans. From that moment, everything would be a race against time to save Drake.

After 28 days of tests, monitors, tubes and wires, Drake was released to go home. There, as Tarah explains, “Our house became a sort of lab.” There were blood tests, feedings, medications and monitoring — day and night, 24/7. Glycine became the O’Sullivans’ obsession as they tried desperately through medication and diet to moderate Drake’s levels. They began to search for information, research, treatment, medical advice — anything to save his life.

The O’Sullivans contacted anyone who might know about NKH, have a related research project or could tell them more. They learned that NKH affects fewer than 500 people worldwide and has no cure. Because there is no medically recognized cure for NKH, all treatments are considered “experimental” and not covered by medical insurance. Period.

So Tarah became a lay scientist. She read everything, called and emailed medical researchers and established the Drake Rayden Foundation to “raise awareness for NKH, fight for better treatment and support research.” She entered a world of genetics and vectors, glycine and metabolic pathways. Tarah had quit college just shy of completing her business degree. Now she desperately needed the scientific expertise that would help her understand the disease and find the cure.

Tarah decided to return to college.

The words “nonketotic hyperglycinemia” meant nothing to Tarah and Eric. But the next words were clear: Drake had a less than 10 percent chance of survival.

BACK TO SCHOOL

With an extremely sick child, three other children at home (expecting a fifth child), sleep deprivation and no scientific background, Tarah found herself at the College of Science open house.

“I met the O’Sullivans at our open house in the fall of 2018,” says Alison Starr-Moss, senior lecturer and academic adviser in the Department of Genetics and Biochemistry. “The moment the presentation was over, Tarah came up to me, introduced herself and told me what she was planning to do.”

Tarah wanted a degree in biochemistry and genetics, and perhaps eventually an advanced degree that would enable her to help those with NKH and other rare diseases. Most immediately, she wanted to save Drake.

College would not be easy. It had been 10 years since Tarah had been in school, and she had taken only basic math and science. Now she would take genetics, bioinformatics, organic chemistry — a host of formidable courses for any student.

But, Tarah was determined. As she told Starr-Moss, “I want to develop technical proficiency and an understanding of genetics and biochemistry and diseases so that I can better help and assist and understand what’s happening with Drake.”

Tarah did not waver. Months later, when she studied in the lab of Kim Paul, associate professor of genetics and biochemistry, Paul saw the same focus: “She wants to have that deep understanding so that she can really speak the language of science to the scientists and to be able to fully, deeply understand the issues and then participate in finding the solutions.”

ON A MISSION

Nonketotic hyperglycinemia is a rare genetic disease. Drake inherited two mutant copies of the gene encoding for an enzyme called glycine decarboxylase — one copy of the gene has a deletion, and the second copy has a missense mutation in the sequence. Drake’s genetic defect reduces his metabolic system’s capacity to break down glycine.

As a building block for protein, glycine is an amino acid that protects the kidneys, transmits chemical signals to the brain and, some believe, may even help prevent cancer. For Drake, the excess glycine accumulates in his blood and spinal fluid, causing severe, uncontrollable seizures that result in injury and malformation of the brain. On an average day, Drake might experience 15 grand mal seizures. When his glycine levels rise dangerously, he can experience 200 or more in a day.

Tarah wanted to know everything about anything that might bring a cure to Drake. She had chosen Clemson, she told Starr-Moss, because of the University’s “understanding of human diseases, the genetics and biochemistry program, and to leverage the faculty expertise and to talk to as many faculty researchers as she could.”

When Starr-Moss heard Tarah’s story, she went to work. “Tarah had learned a lot about the basis of the disease [NKH] but didn’t understand the genetics of the disease,” says Starr-Moss. “She had no math or science. So right away she had to take chemistry, biology and calculus. So Tarah signed up for a full load and started in on those courses.”

Tarah remembers that first encounter with Starr-Moss this way: “She was one of the first people we met at the open house. I talked through my issues, coming in as an older person and with children, with a lot of baggage, with a child who is sick — that’s a lot to take in. But she never hesitated. As soon as she knew what our goals were, she was just, ‘Great, let’s do this. You don’t have time to waste.’ She understood me trying to balance home and school.”

It was Tarah’s first taste of what it meant to be part of the Clemson Family.

The diagnosis was like a starter’s pistol for the O’Sullivans. Everything would be a race against time to save Drake.

STEP BY STEP

When Tarah stepped back into the classroom in January 2019, she wanted hands-on research, and she wanted to start immediately.

As a researcher into canine genetic diseases, Starr-Moss knows firsthand the importance of the research process. Tarah had found her research advocate. “I like to get students into the lab as soon as possible. Even freshmen can get into the research labs,” says Starr-Moss. So, she began at the beginning for Tarah — study of the metabolic process.

Starr-Moss describes the metabolic process like an assembly line. A mutation anywhere along the line stops the process cold. Associate professor Paul describes it this way: “It’s like a Rube Goldberg machine, and one little thing gets off and the whole thing stops. Then you get something like balls piling up representing bad metabolites that do bad things.”

The good news, Starr-Moss says, is that, “We have the ability, in metabolic diseases specifically, to correct underlying defects. If we bypass the broken step in this ‘assembly line’ and put in an intermediate product, then the rest of the pathway can function.” A cure for Drake would involve delivering DNA by way of a carrier called a vector that has been genetically engineered to deliver the gene therapy.

Starr-Moss advised Tarah to join Paul’s lab that was studying metabolism, specifically fatty acid metabolism in African trypanosomes (tropical parasites). Paul knew her research was not an exact fit, but after Tarah emailed her Drake’s story, she knew she had to help. “Even though my research is not on glycine metabolism, we work in metabolism. It is not human metabolism,” says Paul. “But she could learn research protocols for her ultimate goal while learning more about the metabolic process.”

Paul says she found Tarah to be very focused and serious about her work. “She is the most fundamental student. She is here seeking knowledge and experience, which is how universities got started in the first place.”

Tarah jumped into the lab and began learning everything she could about metabolism.

Paul says offering to help Tarah is common at Clemson: “It’s the Clemson Family way of thinking. Family matters a great deal around here, and we try to make adjustments. That concept of family is why, I think, she has gotten so much understanding. It is because the faculty thinks, ‘Oh, I get it. You’re fighting for your kid. We understand. What can we do to help?’”

GOOD ADVICE FROM AN ADVISER

While Tarah was learning the basics of metabolism, Starr-Moss searched across campus for faculty doing research that might be relevant to Tarah’s interests — something she does for all her students.

Starr-Moss heard about Renee Cottle, an assistant professor in the Department of Bioengineering in the College of Engineering, Computing and Applied Sciences. Cottle’s lab focuses on therapies for inherited metabolic diseases that affect the liver, such as familial hypercholesterolemia and hereditary tyrosinemia. Cottle and her team are investigating strategies to overcome technical barriers for advancing a gene therapy for these diseases, including developing methods for delivering gene editing tools into liver cells. 

Tarah contacted Cottle, wanting to learn more about gene therapy. But when Cottle asked Tarah why she was interested in working in her lab, Tarah told her Drake’s story. Cottle asked about how she monitored Drake’s glycine levels and heard how accurately monitoring Drake’s glycine levels was an hour-by-hour issue. For a single glycine test, Tarah would draw Drake’s blood and spin it down. Either she or Eric would then drive the blood to Greenville Memorial Hospital where it was sent to Greenwood Genetic Center. “By the time we get the readings, they are three to four days old. That is if the center is not backed up or the machine is down or it is not the weekend,” says Tarah.

The O’Sullivans consider themselves fortunate to live near one of the three centers in the country that runs the amino acids test. Still, the fact remains that Drake can go into a coma within 48 hours if his levels get high. If his levels are slightly high, he seizes about every three to five minutes for anywhere from 48 hours to four days. Test results that are three to four days old are more like “confirmations” of the adjustments the O’Sullivans have already made based on their observations of Drake. No at-home monitor for testing glycine levels existed, and every company that the O’Sullivans approached about a prototype had declined the request; it simply was not cost-effective to produce.

But Cottle understood. She says Tarah told her an at-home monitor “would be lifesaving because it would allow her to really tailor his diet and the drugs that she’s giving him.”

Cottle then wrote a Creative Inquiry proposal to “develop a low-cost, disposable, stand-alone point-of-care diagnostic and monitoring system to enable caregivers of NKH patients to monitor glycine levels at home, adjust the patient’s drug treatment schedule and improve the patient’s quality of life as well as clinical outcomes.” The proposal was accepted, and in the fall of 2019, Tarah and a team of other undergraduate and graduate students, under the supervision of Cottle, began work to create a “Disposable Point-of-Care Home Testing Platform for Metabolic Disease.”

Tarah says simply, “It will change our lives.”

FAMIILY SUPPORT

With a staggering schedule, Tarah learned to reach out to her professors for help. “I’ve been really impressed with the support above and beyond the classroom,” says Tarah. “I mean the professors — I’ve sat in so many of their offices. I remember sitting in the office of a chemistry professor and talking about an assay I was trying to make work at home, and I couldn’t get the conversions. And he’s trying to make sense of why in the world I was having this trouble.

“And so I explained Drake and our situation and trying to monitor his glycine levels. Finally, the professor said, ‘This is way above your head.’ And I was like, ‘I know. This is way above this class. I need your help.’ He didn’t bat an eye, and we sat there for an hour and a half talking.”

In the fall of 2019, Tarah and a team of other students began working with Professor Cottle to create a disposable home testing platform for metabolic disease.

SO CLOSE

The cure for NKH is simple to say and complicated to do. As Paul says, “First you have to get the fix that will work. And then you have to get the fix to the right location in order for it to work.”

Multiple challenges stand along the way. The single affected gene in NKH can have 400 mutations. Determining exactly what is missing in the gene that carries NKH is painstakingly difficult. Then there are the steps of creating the gene product and developing a vector that will cross the very resistant protections surrounding the brain to reach the affected gene. Any proposed treatment would have to go through multiple levels of testing and clinical trials before approvals. The treatment seemed years away.

But Tarah doesn’t give up. “When you watch a child go through what Drake has gone through for months and now years, you will dig to China if you can figure out a way to help him,” she says.

Tarah located a researcher who had demonstrated success in delivering gene therapy in the treatment of non-NKH metabolic diseases. When she contacted him in 2018, he told her that he was changing research institutions. Tarah agreed to give him a year to get established in his new facility and for the O’Sullivans to determine if gene therapy was the best course forward.

If this researcher thought he would never hear from Tarah O’Sullivan again, he was wrong. One year after her initial contact, she called to tell him Drake was still very much alive, and that their research and observations had convinced them that gene therapy held the greatest promise for a cure. Even though the doctor had a full research agenda, their persistence paid off, and together they made a plan. The O’Sullivans needed to raise $3 million to fund the research project: First, they needed to raise $70,000 to begin research to create the vector for delivery of the gene therapy. In the spring of 2019, Tarah and Eric built a website savingdrake.com that caught the eye of a friend who created a number of billboards in the Greenville area, which in turn caught the eye of television stations WSPA and WYFF who aired the news story. In just 10 days, they raised $70,000, and Tarah, Eric and Drake flew to Texas to meet with the researchers.

After returning, the O’Sullivans are continuing to raise money to begin the laboratory research necessary for FDA approvals in order to move the treatment into patient trials ($300,000 needed) and to begin the clinical trials necessary for final approval of the treatment ($3 million needed).

NEVER GIVE IN

The O’Sullivans’ schedule is exhausting. “We live with a child who is dying every day,” she says. “It is not like Drake is going to be sick one day. He was sick from the moment we brought him home. And he suffers so much. You do that for months on end — all day, all night — up all hours of the night getting meds and trying to make sure he is not choking on seizures. I can only think, ‘You’ve got to do something.’”

For Tarah, that means caring, testing and advocating. It means researching and learning everything she can to do anything she can for Drake and others who suffer without a cure. It means exhaustion and frustration. And it means failure is not an option.

Joquita Burka, a freelance writer in Greenville, is the former director of writing and editing services at Clemson.

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