Hydrocephalus is a life-threatening condition that occurs in about 1 in 1,000 newborns and is often treated with invasive surgery. Now, a new study offers hope of preventing hydrocephalus before it even occurs.
Also known as water on the brain, hydrocephalus is caused by a surplus of cerebral spinal fluid (CSF) that increases pressure inside the skull and can damage brain tissue. About 40 per cent of hydrocephalus cases are caused by single gene mutations which impact the brain's ability to reabsorb CSF fluid.
The most common treatment for hydrocephalus is surgery to create a shunt that drains the fluid. This is invasive and can cause adverse effects such as infection.
To investigate a way to prevent hydrocephalus and eliminate the need for surgery, a research team led by neuroscientist Carl Ernst at The Neuro (Montreal Neurological Institute-Hospital) of McGill University tested whether a drug targeting the mutation itself might stop hydrocephalus.
Ernst and his team used a disease called Schinzel-Giedion Syndrome as an example disorder where many children show hydrocephalus. The syndrome is caused by mutations in a gene called SETBP1, which causes the gene to produce too much protein. The result is a buildup of CSF fluid.
The team gave an oligonucleotide, a type of RNA therapy, to correct the impact of the mutation in mice. They found that oligonucleotide reduced the number of offspring born with hydrocephalus to 25 per cent in newborn mice from 75 per cent in the control group. While the oligonucleotide specifically targeted SETBP1, others may be adapted to treat other mutations, offering potential for a widely used new therapy for genetically caused hydrocephalus.
"The fact that RNA targeting a single gene could have such a major impact on preventing hydrocephalus in mice engineered to have this disease was very shocking to us," says Ernst. "While this condition is unique and very rare, what our work shows for the first time that RNA therapy as a drug class is able to stop hydrocephalus from occurring. Our study opens a whole new therapeutic avenue to start working on hydrocephalus caused by different genes."
This study was published in the journal Molecular Therapy on Jan. 29, 2026. The work was funded by the Sandra and Alain Bouchard Foundation, McGill's D2R, and an EU-JPRD grant funded in part by the Canadian Institutes of Health Research and Fonds de recherche du Québec.
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