Collaboration Propels Research on Untreatable Neurodegenerative Disease

HMS scientists developing novel therapy for specific form of frontotemporal dementia

An overview of antisense oligonucleotides (ASOs) and how they’re used to treat certain genetic diseases. Video: Rick Groleau.

It started with a hunt for lab space and ended with a collaboration born out of what the researchers call a “cosmic coincidence.”

In 2018, Peter Park, professor of biomedical informatics in the Blavatnik Institute at HMS, reached out to his childhood friend and longtime colleague Tim Yu, HMS associate professor of pediatrics at Boston Children’s Hospital. Park’s request was straightforward: Could Yu spare a lab bench to test an idea for a new therapy for frontotemporal dementia (FTD)?

Yu did one better. Park wanted to design a therapy based on short, lab-made genetic sequences called antisense oligonucleotides (ASOs) — and Yu and his team had spent the past six months learning everything they could about ASOs as they raced to build a drug for a little girl with a rare neurodegenerative disease.

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“We just said, ‘gosh, we need to work together on this’ — and so that’s how the project started,” Yu recalled.

“It was an incredibly fortunate coincidence,” Park added.

Now, five years later, Park, Yu, and their teams have developed an ASO that has shown early signs of promise in lab and animal experiments: The molecule appears to increase levels of progranulin, a protein whose production is reduced in the brains of people with the type of FTD that arises from a mutation in a specific gene.