UMass Chan researchers have achieved a gene therapy milestone for a potential treatment of Cockayne syndrome

Researchers working with the UMass Chan School of Medicine’s Translational Institute for Molecular Therapy report progress in developing a vector to deliver gene replacement therapy in mouse models of Cockayne syndrome, a rare and fatal neurodegenerative disease that largely affects children and young adults.

This proof-of-concept milestone for an adenovirus (AAV) vector gives hope to parents like Jo Kaur and Richard DiGeorge of New York, who are desperate to get a cure for their child. The couple founded a nonprofit organization, the Ryan Research Initiative, and entered into an agreement with UMass Chan in 2021 to support research after their son, Ryan, was diagnosed with a fatal autosomal recessive disorder.

Ana Rita Batista, PhD, instructor in neuroscience, is leading the research, along with Miguel Sina Esteves, PhD, assistant professor of neuroscience and director of the Translational Institute for Molecular Therapeutics.

“It’s very exciting,” Core said. “This development gives us so much hope and hope that we can translate this treatment that we’re seeing work in mice to kids like Ryan and others around the world who are suffering and don’t really have much choice. Thanks to the very enthusiastic and smart UMass Chan team, we’ve reached a major milestone for the Cockayne Syndrome community.” In a very short time.”

“We now have AAV vectors that have a profound impact on survival in animals, and now it appears to be normal, treated ones,” said Dr. Sina Estevez. “So, progress has been very good. And obviously, ultimately our goal is to move toward clinical trials.”

Dr. Batista explained that Cockayne syndrome is caused by genetic mutations in the ERCC8 (CSA) or ERCC6 (CSB) genes. The most common feature of the disease is the small size of the child. Many have developmental delays and problems with vision and hearing, among other things, but there is a wide range of effects.

“What we’re working on now is developing a gene therapy approach where we’ll give these patients a normal, functional gene for CSA that will hopefully improve their lives,” Batista said.

The research team reported that in preliminary studies they extended the lifespan of animal models, which resumed normal growth after treatment, according to Sina Estevez.

He pursued cures for breakneck diseases like cocaine – which afflict fewer than 5,000 people in the United States According to the National Institutes of Health– It is difficult to make a commercial case due to the high cost of research and development with relatively low expected market returns. This is why partnerships with family fundraising organizations such as the Ryan Research Initiative are so important.

The Translational Institute was launched in 2022 to streamline the process and reduce upfront costs associated with developing gene therapies for rare diseases.

“This is kind of a pipeline that we’re building and putting in place so that we can move these therapies faster into the clinic,” said Sina Estevez. “Proof-of-concept experiments in mice are necessary to show us that it is worthwhile going forward.”

Meanwhile, 3-year-old Ryan gives a personal face to scientists as they search for effective treatments. He’s smart, energetic, and loves playing soccer with the walking trainer and listening to Sesame Street and Cocomelon songs, according to his parents. “Most people think, ‘He has a rare disease, and he’s not going to be able to do certain things,’ but it’s actually the opposite,” DeGeorge said.

While one of the goals is to build capacity through the institute, Sena-Esteves said, “Mostly, the goal is to serve the rare disease community, so we can make an impact and change the paradigm in which this works a little bit, this translation from the bench to the clinic. Unless Something changes, these diseases will be left behind.

Related UMass Chan news stories:
The Ryan Research Initiative funds gene replacement therapy research for Cockayne syndrome at the UMass Chan School of Medicine
UMass Chan launches Translational Institute for Molecular Therapy

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