
Every biomedical scientist dreams of playing a role in a medical miracle, but few have the privilege of seeing their work advance to that level within their lifetime.
One exception is Dr. Scott Dindot, a professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (VMBS) Department of Veterinary Pathobiology and the executive director of molecular genetics at Ultragenyx, a biopharmaceutical company.
For more than 20 years, Dindot has studied Angelman syndrome (AS), a rare genetic disorder that affects approximately 1 in 15,000 live births per year and is usually diagnosed when a child is 2 to 3 years old.
Individuals with AS typically have severe developmental delays, absent speech, movement and balance issues, and frequent seizures. Currently, there are no approved drug therapies for AS, and the standard of care is focused on behavioral therapy and controlling specific symptoms, especially seizures.
But soon, that may change.
In 2017, Dindot invented a compound called GTX-102 that targets the genetic cause of AS — loss of the maternal copy of the UBE3A gene. Individuals with AS have genetic mutations that lead to the loss of maternal UBE3A — to replace it, GTX-102 “turns on” the paternal copy of the same gene, which is usually silenced.
Last year, the therapy achieved two big milestones on its path to to U.S. Food & Drug Administration (FDA) approval — over the summer, GTX-102 received FDA Breakthrough Designation and a generic drug name, apazunersen, and at the end of last year, Ultragenyx, the biopharmaceutical company developing GTX-102, announced the global expansion of the therapy’s phase 3 human clinical trial.
If the trial is successful, and if the drug is subsequently approved by the U.S. Food and Drug Administration, it will be the first drug therapy for AS and the first FDA-approved drug to come from Texas A&M.
A Chance Partnership
Dindot never planned on studying AS — like many scientists, his choice of focus developed over time through graduate school and postdoctoral training.
One defining experience was working as a postdoc in the lab of Dr. Arthur Beaudet, a professor of molecular and human genetics at Baylor College of Medicine, who was instrumental in discovering AS’ genetic cause.
“When I started my faculty profession at Texas A&M, I continued to do work on AS,” Dindot said. “I was very interested in how the UBE3A gene is regulated in the brain.”
Meanwhile, an organization run by parents of children with AS called the Foundation for Angelman Syndrome Therapeutics (FAST) was looking for research partners.
“They didn’t want the usual academic cycle of doing research, publishing papers, and training students; they wanted a therapy for AS,” Dindot said. “At the time, it wasn’t very common for parents and foundations to get involved with developing therapies, but we’re actually starting to see that change because of FAST and similar organizations.”
In 2012, Dindot was asked to join a consortium funded by FAST that would try to develop a drug therapy for AS. For six years, he and four other scientists from three other institutions tried every means at their disposal to find some way to treat it directly.
“Every Friday for six years we met on Zoom with parents from FAST,” Dindot said. “They held us accountable; we gave them updates on what we had found and what we were doing, and we explored a lot of things. We looked at drugs that were already approved by the FDA, gene therapies, our own research, everything.”
Dindot’s project — turning on the paternal copy of UBE3A — was one that worked.
“Because of FAST, I knew the kids and their parents and what it was like for them. It was incredibly motivating,” he said. “Interacting with the children, their families, and caregivers was incredibly meaningful. They reminded us why our research matters and inspired us to explore every possible path to make a difference.”
The Science Of Gene Regulation

What makes GTX-102 such a unique discovery is its ability to target the root cause of AS rather than treat its symptoms. Because AS is caused by a genetic mutation, impacting the root cause — the loss of UBE3A — is no small feat.
All individuals carry two copies of UBE3A, but in the brains of healthy individuals, only the maternal copy is expressed — or “turned on” — while the paternal copy is “off.” When the mutation causing AS occurs, it silences the maternal copy, leaving no version of the gene expressed, Dindot said.
A single gene turning off may not sound like a major problem, but genes determine everything from easy-to-spot physical traits, like a person’s hair color, to more complex bodily systems, like the immune system.
The human genome contains around 20,000 genes and a single gene’s expression may influence dozens of others in a complicated pattern of gene relationships. This is why individuals with AS experience changes to so many aspects of life, all caused by the loss of a single gene.
To solve the problem, GTX-102 uses synthetic molecules of DNA and RNA to turn off the gene that silences the paternal copy of UBE3A, allowing it to replace the missing version.
“GTX-102 is unique not only because it targets the genetic cause of AS but also because it’s the first disease-modifying drug for AS to advance into clinical development,” Dindot said. “There are only a few examples of disease-modifying drugs being used to treat genetic disorders and even fewer examples that are being developed to treat neurodevelopmental disorders such as AS.”
Leading The Way Forward
While the primary outcome of Dindot’s research is the discovery of GTX-102 and its significance for the AS community, his work has also had a positive impact on the next generation of genetic researchers.
Former VMBS graduate trainee Dr. Ryan Doan is now an assistant professor of pediatrics at Boston Children’s Hospital and Harvard Medical School. During his time in Dindot’s lab at Texas A&M, Doan learned cutting-edge techniques — and developed some of his own — that have been formative for his own research career, which focuses on the genetic mechanisms behind complex disorders like autism spectrum disorder and attention-deficit/hyperactivity disorder.
“Many of the methodologies that I use today are similar to what we used when I was working on my Ph.D.” Doan said. “Although most of my work in Dr. Dindot’s laboratory focused on other areas, my contributing to an early study from his lab examining how imprinting affects UBE3A dosage in neurons sparked my lasting interest in brain disorders and inspired me to apply my skills to conditions such as autism.”
Doan’s career success includes a major discovery — that there is a genetic cause for ADHD — which has allowed Doan to give answers to families who have long wondered why their children have the condition. In the future, it may even lead to new treatments.
Clinical Trials Continue
While it has taken over a decade of hard work for Dindot’s research to arrive at its current stage, the last several years have seen many leaps forward.
In late 2017, once enough data had been collected to show the potential of Dindot’s discovery, FAST formed a company called GeneTx Biotherapeutics LLC that would develop the treatment for a phase 1/2 clinical trial. In 2022, the company was purchased by Ultragenyx, which now leads the development of GTX-102.
The phase 3 clinical trial is currently ongoing, and participants are being dosed. Hopefully, the results will show that GTX-102 is ready to move forward to the next stage of development — going through a rigorous approval process prior to becoming available to families.
In the meantime, GTX-102 has already received its official FDA name — apazunersen — and a Breakthrough Therapy designation, a process designed to expedite the development and review of drugs that are intended to treat a serious condition after preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy, according to the FDA.
Both steps increase the likelihood of FDA approval.
“It’s been a team effort the entire journey,” Dindot said. “It wouldn’t have happened without the families, FAST, GeneTx, Ultragenyx, or the many amazing trainees who have worked in my lab over the years. They each have played a major role in the success of this project.”
For more information about the trial, visit the clinical trial’s website at tx.ag/ASClinTrial or contact Ultragenyx at trialrecruitment@ultragenyx.com.
GTX-102 is an investigational [antisense oligonucleotide (ASO) OR therapy] that is not currently approved by any health authority.
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Note: This story originally appeared in the Summer 2025 issue of VMBS Today.
For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on Facebook, Instagram, and Twitter.
Contact Information: Jennifer Gauntt, Director of VMBS Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences, jgauntt@cvm.tamu.edu, 979-862-4216
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