UMass Chan licenses gene therapy for rare genetic disorder to Raiden Science Foundation

UMass Chan Medical School has licensed an adeno-associated virus (AAV) gene therapy to the Raiden Science Foundation (RSF) to develop a clinical treatment for UBA5 disorder.

“The Raiden Science Foundation has been instrumental in propelling academic research into UBA5 disorder forward,” said lead investigator Toloo Taghian, PhD, assistant professor of genetic & cellular medicine and radiology at UMass Chan. “Without their support and backing we couldn’t have reached this important milestone. We are excited to be working with such highly motivated and skilled professionals at RSF and look forward to the next steps of clinical development for a gene therapy product.”

“By working together with families and foundations, like the Raiden Science Foundation, we can build a pipeline that seamlessly moves fantastic basic science research toward new treatments and clinical trials with regulatory support for patients suffering from rare genetic diseases,” said Miguel Sena-Esteves, PhD, associate professor of genetic & cellular medicine and neurology and director of the Translational Institute for Molecular Therapeutics (TiMT) at UMass Chan.

Established in 2022, the TiMT was formed to leverage UMass Chan’s extensive experience in researching gene therapies to develop early-stage clinical trials for patients suffering from rare genetic diseases. The institute includes infrastructure to assist investigators with manufacturing, regulatory matters and the drug-enabling studies needed to conduct first-in-human clinical trials. This allows the TiMT to reduce the costs associated with human gene therapies while increasing the number of clinical trials for rare genetic diseases.

UBA5 disorder (also known as developmental and epileptic encephalopathy 44 or DEE44) is a life-threatening, progressive neurological disorder that typically manifests in infancy. The UBA5 gene encodes for a protein crucial for ufmylation, a fundamental process in cellular homeostasis, maintaining protein balance and protecting neurons from stress. UBA5 disorder occurs when mutations in the UBA5 gene cause a deficiency in normal UBA5 gene activity leading to protein malfunction, cell toxicity and neuron death resulting in neurodevelopmental impacts and reduced neuronal function. There is no known cure for UBA5 disorder. With fewer than 100 cases diagnosed worldwide, managing symptoms is the only available treatment option.

“UBA5 disorder steals development, movement and childhood,” said Tommy Pham, co-founder and president of RSF and father of 5-year-old Raiden who was diagnosed with UBA5 disorder in 2021. “It is a single-gene disorder with no approved FDA treatments or cures, making it well suited for gene therapy interventions.”

Tommy and Linda Pham founded the Raiden Science Foundation to advance research and treatment for the disease soon after learning Raiden had UBA5 disorder. In 2022, the foundation jump-started research into a gene therapy treatment with an initial donation to a team of UMass Chan investigators including Dr. Sena-Esteves, Dr. Taghian and Heather Gray-Edwards, DVM, PhD, assistant professor of genetic & cellular medicine.

Since then, through additional funding from the Raiden Science Foundation, the UMass Chan team has developed a UBA5 targeted AAV9 vector that could potentially deliver a corrective copy of the UBA5 gene to patients, thereby restoring normal cell function. Once it was shown to be effective in preclinical mouse models, the potential therapy was submitted by UMass Chan for a pre-investigational new drug package to the Food and Drug Administration in late 2025.

“Now that we have guidance from the FDA, we look forward to starting the clinical development second phase of this program in partnership with RSF, in hopes of initiating as soon as possible a first-in-human phase I/II AAV gene therapy clinical trial to be conducted at UMass Chan,” said Sena-Esteves.

“For patient-led, nonprofit organizations like RSF, the whole purpose of funding university academic research is to develop a therapy,” said Chris Andon, executive director of the Raiden Science Foundation. “The license agreement with UMass Chan provides us with a strong collaborative framework around development timelines, intellectual property and funding opportunities with the aim of bringing a treatment to patients with this horrible disease,” said Andon.