When Susan Stewart's son, Eric, was 2 years old, she noticed his speech wasn't developing like her two older sons. Concerned, she took him to a doctor but was told not to worry.
Later, she took him to an audiologist, thinking the problem might be his hearing. Eric was nonverbal and behind developmentally.
As Eric got older and entered school, he started having seizures. He was diagnosed with autism and placed in special education classes. Over time, Stewart watched helplessly as Eric's health worsened. At age 11, Eric developed juvenile cataracts, and a subsequent visit to a neurologist didn't offer any answers.
"He was in a wheelchair by age 14," Stewart said. "I saw him dying before my eyes. We had to stop Special Olympics because he didn't have the energy anymore."
Desperate for answers, Stewart searched the internet. Eventually, she found information about Smith-Lemli-Opitz syndrome, a rare genetic disorder caused by a cholesterol synthesis defect, which leads to intellectual and developmental problems. Stewart reached out to a leading expert on this syndrome, William E. Connor, M.D., a physician-scientist at Oregon Health & Science University from 1975 until he passed away in 2009, who was conducting pioneering research with his wife, Sonja Connor, R.D., M.S., on rare diseases linked to abnormalities in cholesterol and related sterol molecules — a type of lipid. She has continued to be involved with the research since 2009.
A series of tests measuring abnormal sterol biomarkers of the disease led to a diagnosis at age 16: Eric had cerebrotendinous xanthomatosis, known as CTX, a rare recessive, inherited disorder that affects the body's ability to metabolize cholesterol and results in the accumulation of sterol molecules. Symptoms of CTX include chronic diarrhea from birth, juvenile cataracts, seizures, developmental delays, and intellectual disability. As the disease progresses, patients may develop tendon xanthomas — which are sterol deposits in tendons — and neurological issues like cognitive decline and dementia.
The Connors' research at OHSU built the foundation for the next generation of OHSU researchers to identify biomarkers essential to identifying and treating CTX. The decades of discovery led to a clinical trial at OHSU, and in February culminated in Food and Drug Administration approval of a treatment pioneered at OHSU. Next for the research team is pushing to test for the biomarker in newborns, so that more people can receive effective treatment before the disease progresses.
For Eric, Connor recommended treatment with chenodeoxycholic acid, which was approved for gallstones but shown to help with the treatment of CTX.
"At the time, it wasn't even made in the U.S., so I had to pay for it out-of-pocket from England," Stewart said. "Eventually it became available in the U.S., but we had to fight to get it covered because it was off-label usage."
Now 34, Eric no longer uses a wheelchair. The medication has helped him regain some independence: He can get himself a glass of water, bowl and play his favorite arcade games. He is still nonverbal and lives in a group home in Salem, but his quality of life has vastly improved, and the disease progression has stopped.
Building biomarker tests
For the past decade, Andrea DeBarber, Ph.D., research associate professor in the OHSU School of Medicine, has continued the work the Connors started, developing better ways to identify CTX with biomarker tests and pushing for FDA approval of the treatment.
DeBarber oversees bioanalytical services provided through core facilities at OHSU, acting as the technical supervisor of the OHSU Sterol Analysis Laboratory core, an accredited laboratory that provides clinical biomarker testing. She started research on developing improved screening and diagnostic biomarker tests for CTX with Connor in 2010, and took over the laboratory in 2013 to make the new biomarker tests available as part of clinical care provided to patients with CTX.
In 2019, the Sterol Analysis Laboratory was the first lab in the country to offer sensitive testing to measure a bile alcohol biomarker in the urine of CTX patients, improving the ability to diagnose and treat patients with CTX. Bile is produced by the liver and allows the body to process fats and cholesterol. Researchers discovered that some patients with CTX may have a normal screening test result for plasma cholestanol — measuring sterol levels in the blood plasma — but the bile alcohol concentration will be abnormal, thereby identifying the difficult-to-diagnose disease.
Still, patients struggled to get a diagnosis of CTX, and once diagnosed, to access chenodeoxycholic acid therapy because it was listed as off-label.
"This drug has been the standard of care for CTX for the last 40 years or so," DeBarber said. "It replaces the missing bile acid in people with CTX, it normalizes their biomarker levels, and stabilizes or improves clinical manifestations, preventing further disease progression."
The first clinical trial
In 2020, the OHSU Sterol Analysis Laboratory partnered with a pharmaceutical company for a major clinical trial, the RESTORE study, to gather data for FDA approval of chenodeoxycholic acid for CTX. The trial, sponsored by Mirum Pharma, was the first of its kind and used data from OHSU's biomarker tests.
In February 2025, based on the clinical trial results, the FDA approved the drug, now marketed as Ctexli, as a treatment for CTX.
Igor Landais, Ph.D., a quality assurance expert at the OHSU Vaccine & Gene Therapy Institute, ensured that all trial work at OHSU met FDA standards, helping make the approval possible.
"This achievement was made possible by the Sterol Analysis Laboratory's work over the last 10 years to develop sensitive tests for CTX biomarkers," Landais said. "OHSU's is the only lab in the world that could perform some of these tests to the exacting standards required by the FDA."
P. Barton Duell, M.D., professor of medicine in the OHSU School of Medicine and director of the Sterol Analysis Laboratory since 2005, collaborated to oversee the clinical trial. He is an endocrinologist and lipid specialist in the section of preventive cardiology at OHSU. He has been treating patients with rare lipid disorders, including CTX, and participating in studies of these conditions for several decades. He started working with Connor in 1990, and took over the longstanding institutional review board-approved study of the effects of diet and medication in CTX in 2009. He is also Eric's physician.
"The results of the RESTORE study provided critical data that convinced the FDA to approve chenodeoxycholic acid for treatment of CTX," he said. "Our ongoing quest is to facilitate early diagnosis and treatment of CTX and other rare disorders to prevent complications and improve quality of life. We will continue to conduct clinical studies and participate in outreach activities to help ensure these important goals can be accomplished."
Andrew Chitty, M.B.A., is director of OHSU's University Shared Resources program. He said core labs under the program, like the Sterol Analysis Laboratory, can benefit from working with external industry partners.
"Supporting this clinical trial allowed the core to build critical infrastructure at OHSU, including obtaining analytical instruments required for human clinical trials," he said. "This is one example of how the external work in cores can strengthen shared resources available for our research community."
Next goal: Screening newborns
However, for Stewart, DeBarber and Duell, the fight is not over. All three are members of the CTX Alliance, which is advocating for CTX to be placed on the list of newborn screening conditions from the Recommended Uniform Screening Panel, or RUSP. The RUSP gives federal guidelines for state newborn screening programs, aiming to ensure every newborn is screened for conditions with the potential for early intervention and treatment.
DeBarber has collaborated with Michael Gelb, Ph.D., at the University of Washington, and colleagues in the Netherlands, to develop biomarker testing that can screen newborns for CTX. With a test that can identify CTX in newborns and the approval of Ctexli, a team led by DeBarber is planning to present new data to advocate for CTX to be added to the RUSP.
"Some of the infants who have CTX die very early of liver disease, and others slowly progress until they are in their 30s or 40s," Stewart said. "It's a horrible disease, but it's treatable now. No children should have to suffer the way Eric did."
Stewart's journey with her son also gave her insight into the power of dedicated complex care at OHSU and the value of clinical trials. A few years ago, she was diagnosed with a rare eye melanoma and is now involved in a clinical trial for it in San Francisco.
"I'm grateful to OHSU for finally solving the puzzle that was my child," Stewart said. "When my local doctor couldn't figure out what was happening with my eye, I went straight to OHSU and got involved in clinical trials. I've learned a lot about advocacy and finding help through trials."
DeBarber says that getting CTX added to the RUSP and newborns screened for CTX will be critical to identify CTX early.
"It's heartbreaking to see children and adults who had to wait too long for a diagnosis or who've been misdiagnosed and whose disease has progressed too far," she said. "We want to try and make sure every patient has access to early diagnosis and treatment and that no one has to suffer from the effects of CTX disease progression again."
DeBarber would like to acknowledge the critical role that Sonja Connor, M.S., and the Sterol Analysis Lab staff team, Gladis Reyes Pimental, B.S., Maya Fowler, B.S., Jenefer DeKoning, Ph.D., and former lab member Samantha Redder, B.A., played in providing laboratory testing for the RESTORE study.
In our interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. With regard to this research, DeBarber serves as a volunteer Medical and Scientific Advisory Board member for the CTX Alliance and the United Leukodystrophy Foundation. DeBarber has consulted for Leadiant Biosciences, Retrophin/Travere and Mirum Pharma. Duell serves as an advisor for Ionis, Mirum, New Amsterdam, Novo Nordisk, and Regeneron. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere and he serves as a volunteer Medical and Scientific Advisory Board member for the CTX Alliance.
The OHSU Foundation and OHSU Departments have received gifts from Travere (now Mirum). These gifts, which have not been made specifically in connection with this research, have been reviewed by the OHSU integrity office. Review details of OHSU's conflict of interest program to find out more about how we manage these business relationships
The Phase 3 clinical trial, RESTORE, was funded by Mirum Pharma as a fee-for-service contract with OHSU.
