Melissa Barker-Haliski’s work at the UW School of Pharmacy is exploring whether emerging gene therapy approaches for DRPLA could help reduce seizures and improve daily life for patients and families.
For families living with dentatorubral-pallidoluysian atrophy, or DRPLA, so much of life can be shaped by uncertainty.
The ultra-rare inherited disorder progressively worsens movement, coordination, cognition and mood. In some patients — especially children — it also brings treatment-resistant seizures, adding disruption and fear to lives already marked by a difficult diagnosis.
At the University of Washington School of Pharmacy, Department of Pharmaceutics and Plein Center Associate Professor Melissa Barker-Haliski is part of a growing global effort to better understand whether emerging gene therapy approaches for DRPLA could help address one of the disease’s most difficult and visible symptoms: seizures.
What started as first an effort by the Cure DRPLA Foundation to produce a good preclinical model of DRPLA to understand why the disease occurs has transitioned into an international effort to modify the burden of seizures in DRPLA. Dr. Barker-Haliski’s lab is now building on their earlier work with this mouse model to more closely understand seizure susceptibility and progression in DRPLA. Her lab wants to ask an important question: if a gene therapy can target the disease processes itself, might it also lessen some of the symptoms that most affect everyday life?
“Epilepsy is a spectrum. Many different causes lead to seizures but oftentimes, these causes require tailored treatments to get the symptoms under control. Every case of epilepsy is an opportunity to integrate precision medicine practices for optimal management. Through this project, my lab is diving deeper into defining the biological underpinnings of seizure susceptibility in DRPLA,” Barker-Haliski said, “to know whether use of a new gene therapy can modify seizure and epilepsy-related symptoms of DRPLA.”
The work comes at a time of growing momentum in the field. Gene therapies are on the horizon for several different ultra-rare epilepsies and DRPLA is no exception. An investigational gene therapy for DRPLA is already being tested in a single-patient clinical trial, and researchers are continuing to build the evidence needed to understand how similar approaches may affect genetic causes of epilepsy, more broadly.
Barker-Haliski’s research, supported by the American Epilepsy Society and Cure DRPLA, was showcased at the American Epilepsy Society’s annual meeting in December 2025 and at the American Society for Pharmacology and Experimental Therapeutics’ annual meeting in May 2026. Now, a new NIH-supported collaboration with the Korecka lab at Harvard is helping to deepen that work, with researchers examining the disease-modifying potential of gene therapies and the cellular changes that may follow treatment in human patient-derived reprogrammed neurons.
“Our new NINDS grant hopes to demonstrate that seizure susceptibility can be minimized with this gene therapy,” Barker-Haliski said. “We are collaborating with the Korecka lab to use isolated patient skin cells that have been reprogrammed into neurons to investigate how cellular changes affect the likelihood that brain cells will be more hyperexcitable and thus prone to seizures and epilepsy. We hope that this work will uncover new therapeutic opportunities for people with DRPLA to better manage their seizure symptoms and long-term prognosis.”
Rare-disease research often moves step by step: carefully, collaboratively, and with patience. But each step can matter. Each finding adds to a fuller understanding of the disease and of what future treatment might look like.
For people living with DRPLA and for the families who care for them, that work is about more than scientific progress alone. It is about the possibility of a life with fewer seizures, greater stability and, over time, a clearer path forward.