An Oregon couple whose baby was diagnosed with an ultra-rare genetic disorder has launched a foundation to raise money to accelerate development of therapies for the condition, called UBA5 deficiency, and recently signed a gift agreement with UMass Chan Medical School for $85,000 to jump start the research.
The , founded by Tommy and Linda Pham on behalf of their nearly 2-year-old son, Raiden, plans to raise $3 million more for the project, which supports research in UMass Chan’s newly created .
Looking at Raiden Pham sitting peacefully in his mother’s arms, one wouldn’t guess the toddler has a disease that is robbing him of motor control and stunting other areas of growth. UBA5 disorder, a life-threatening progressive neurological disorder, typically involves muscle floppiness as well as stiffness, seizures, movement disorder, brain abnormalities, intellectual disability, poor head growth and failure to thrive. Caused by a gene mutation, there are only around 30 known cases in the world.
Raiden is the Pham’s second child. Initially, he hit normal development milestones. “Then after three months, we noticed something changed, like he wasn’t progressing,” said Linda Pham. Raiden couldn’t keep nourishment down and often seemed in pain.
The Phams soon started an intensive medical journey involving hospitalizations, gastric-feeding tube insertions and genetic testing. In August 2021, Raiden’s genomic sequencing pointed to the UBA5 deficiency.
With a background in biotech, Tommy Pham delved into papers on gene therapy. “Once we knew about gene therapy, even though a lot of it is experimental, it provides hope,” he said. “I reached out to a few contacts of mine, both on the West Coast and the East Coast.” They gave him the names of top researchers in the field.
“I reached out to everyone, and (Dr.) Miguel (Sena-Esteves) and Dr. (Guangping) Gao were the first ones to get back to us,” Tommy Pham continued. “The UMass team is like an all-star research team with years of knowledge and experience in the field of gene therapy that will give this the best chance at succeeding.”
“We’re actually beginning to have opportunities to design therapies for individual children, or at least for children with entire groups of genetic mutations that might be able to be treatable by gene therapy,” said Terence R. Flotte, MD, the Celia and Isaac Haidak Professor, executive deputy chancellor, provost and dean of the T.H. Chan School of Medicine.
“It’s a hopeful time but also a time where we’re somewhat on the precipice because the clock is ticking, and the child may have a condition that continues to progress as we’re working on the research. That makes it all the more crucial that we accelerate translating knowledge about what the gene is into some form of therapy,” he said.
The was formed to address just this type of need. Families who have a child with a rare disease have few options because not much may be known about the genetic mutations associated with the disease; and because it is rare, funding opportunities for developing treatments is limited.
“The Institute came about with the recognition that we have fantastic basic research, but then we don’t have an outlet for it, and investigators have to do a lot of work themselves to make it go from the bench discovery to the clinic,” said Miguel S. Sena-Esteves, PhD, associate professor of neurology and director of the Translational Institute. “We want to establish a pipeline that moves the program seamlessly from the discovery all the way to the clinical trials and having regulatory support.”
Dr. Sena-Esteves said that this streamlined translational approach will be less costly than nonintegrated research and therapeutic development models, which will ultimately lower the entry barrier into clinical trials.
Another goal of the Institute, Sena-Esteves said, is to train young faculty who can do translational research in partnership with families.
Provost Flotte said the four key components of the Institute are to establish proof of concept to identify the gene and create a replacement tool; conduct preclinical proof-of-concept animal studies to determine dose, delivery mechanism and toxicities, while coordinating progress with the Food and Drug Administration; manufacture patient-grade material to deliver the gene therapy; and specify clinical trial protocol and outcomes.
After the therapy is tested in a human, he said, “A smooth handoff to an industry partner is much more likely.”
The first step, establishing proof of concept, is typically covered by research grants. But the next three steps are “incredibly expensive and have in the past been very time consuming. And the time part is really the concerning part,” said Flotte.
Research on UBA5 supported by the Raiden Science Foundation is led by Heather Gray-Edwards, DVM, PhD, assistant professor of radiology, and Toloo Taghian, PhD, instructor in radiology, who work with Sena-Esteves and others across several departments.
Tommy Pham said fundraising that they are doing for a UBA5 therapy is significant, but they remain undaunted. “We feel confident that UMass is the right choice to be on this journey with us.”
Connecting with other families with rare diseases, who may benefit from future breakthroughs in gene therapy, also inspires the Phams. They believe that their efforts are enabling a platform for the future of personalized medicine that will help treat countless rare diseases in the future.
“We honestly don’t want another family to go through what we went through, so if we can help in any way, that’s a win for all of us,” said Linda Pham.