Hydrocephalus is a life-threatening condition that occurs in approximately 1 in 1,000 newborns and is often treated with invasive surgery. Now, a new study offers hope of preventing hydrocephalus before it even happens.
Also known as water on the brain, hydrocephalus is caused by excess cerebrospinal fluid (CSF) that increases pressure inside the skull and can damage brain tissue. About 40 percent of hydrocephalus cases are caused by unique genetic mutations that affect 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 side effects such as infection.
To study a way to prevent hydrocephalus and eliminate the need for surgery, a research team led by neuroscientist Carl Ernst of The Neuro (Montreal Neurological Institute-Hospital) of McGill University tested whether a drug targeting the mutation itself could stop hydrocephalus.
Ernst and his team used as an example a condition called Schinzel-Giedion syndrome in which many children have hydrocephalus. The syndrome is caused by mutations in a gene called SETBP1, which cause the gene to produce too much protein. The result is a buildup of CSF fluid.
The team administered an oligonucleotide, a type of RNA therapy, to correct the impact of the mutation in the mice. They found that the oligonucleotide reduced the number of offspring born with hydrocephalus to 25 percent in newborn mice, compared to 75 percent in the control group. While the oligonucleotide specifically targeted SETBP1, others could be adapted to treat other mutations, providing the potential for a new, widely used therapy for genetically induced hydrocephalus.
The fact that an RNA targeting a single gene could have such a significant impact on preventing hydrocephalus in mice engineered to suffer from this disease really shocked us. Although this condition is unique and very rare, our work shows for the first time that RNA therapy as a class of drugs is capable of preventing hydrocephalus from occurring. Our study opens a whole new therapeutic avenue to start working on hydrocephalus caused by different genes. »
Carl Ernst, neuroscientist, Montreal Neurological Institute-Hospital of McGill University
This study was published in the journal Molecular therapy on January 29, 2026. The work was funded by the Sandra and Alain Bouchard Foundation, McGill D2R and an EU-JPRD grant funded in part by the Canadian Institutes of Health Research and the Fonds de recherche du Québec.
