Researchers working with the Translational Institute for Molecular Therapeutics at UMass Chan Medical School have announced progress in developing vectors to deliver gene replacement therapy in a mouse model of Cockayne syndrome. Cockayne syndrome is a rare and fatal neurodegenerative disorder that greatly affects children and young adults.
The adeno-associated virus (AAV) vector proof-of-concept milestone gives hope to parents such as Jo Kaur and Richard DiGeorge of New York who are desperately searching for a cure for their children. The couple founded the nonprofit Riaan Research Initiative, and in 2021 he signed a deal with UMass Chan to help research after his son, Riaan, was diagnosed with a fatal autosomal recessive disorder. .
Neurology instructor Ana Rita Batista, Ph.D., is leading the research, along with Miguel Sena Estevez, Ph.D., associate professor of neurology and director of the Translational Institute for Molecular Therapeutics.
“It’s very, very exciting,” said Kaur. “This development holds a lot of promise and hope that we can translate that therapy that we see working in mice to Riaan and other children around the world who are suffering and really don’t have many options. Thanks to the highly motivated and talented UMass Chan team, we were able to reach a landmark milestone for the Cockayne Syndrome community in a very short period of time.”
“We now have AAV vectors that actually have a significant impact on animal survival, and now they appear to be normal and cured,” said Dr. Sena-Esteves. “So progress is very good. And obviously our ultimate goal is to move into 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 this disease is the child’s very small size. Many people have developmental delays, vision and hearing problems, but the range of effects is wide.
“What we are currently working on is developing a gene therapy approach in which we hope to give these patients a functioning CSA gene and improve their lives.” said Batista.
According to Sena-Esteves, the research team reported in early studies that it extended lifespan in animal models and resumed normal growth after treatment.
According to the National Institutes of Health, treatments for ultra-rare diseases such as cockaine, which affect fewer than 5,000 people in the United States, are expensive to research and develop and have relatively low expected efficacy, making them commercially viable. It’s hard to make an argument, he continued. Market Earnings. That’s why partnerships with family fundraising organizations such as the Riaan Research Initiative are so important.
The Translational Institute will be launched in 2022 to streamline the processes and reduce initial costs associated with developing gene therapies for rare diseases.
“This is kind of a pipeline that we are building and putting in place so that we can move these therapies into the clinic more quickly,” said Sena-Esteves. “Proof-of-concept experiments in mice are needed to prove it’s worth moving forward.”
Meanwhile, 3-year-old Riaan provides a personal face to scientists searching for effective treatments. According to his parents, he is bright and energetic and loves playing football with his gait trainer and listening to songs by Sesame Street and Cocomeron. “Most people think he can’t do certain things because he has a rare disease, but it’s actually the opposite,” DiGeorge said.
Sena-Esteves says one of the goals is to create capacity through the Institute, but “most of the goals are to serve the rare disease community, so to have an impact and change a little bit the paradigm in which this works. We can bench to the clinic. Unless something changes, these diseases will be left behind.”
Related UMass Chan news articles:
Riaan Research Initiative Funds Cockayne Syndrome Gene Replacement Therapy Research at UMass Chan Medical School
UMass Chan Founds Translational Institute for Molecular Therapeutics