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 for preventing hydrocephalus before it even occurs.
Also known as water on the brain, hydrocephalus is caused by an excess of cerebrospinal fluid (CSF) that increases pressure inside the skull and can damage brain tissue. About 40 percent of hydrocephalus cases are caused by single gene mutations that affect the brain’s ability to reabsorb CSF fluid.
The most common treatment for hydrocephalus is surgery to create a drain that drains the fluid. This is invasive and can cause side 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 McGill University’s The Neuro (Montreal Neurological Institute-Hospital) tested whether a drug that targets the mutation itself could stop hydrocephalus.
Ernst and his team used a disease called Schinzel-Giedion syndrome as an example of a disorder where many children develop hydrocephalus. The syndrome is caused by mutations in a gene called SETBP1, which cause the gene to make too much of the protein. The result is the accumulation of liquid CSF.
The team gave an oligonucleotide, a type of RNA therapy, to correct the impact of the mutation in mice. They found that the oligonucleotide reduced the number of offspring born with hydrocephalus to 25 percent in the newborn mice from 75 percent 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 treatment for genetically induced hydrocephalus.
The fact that RNA targeting a single gene could have such a significant impact on preventing hydrocephalus in mice engineered to suffer from this disease was very shocking to us. Although this condition is unique and very rare, what our work shows for the first time is that RNA therapy as a class of drugs can stop the occurrence of hydrocephalus. Our study opens up a whole new therapeutic avenue to start working on hydrocephalus caused by different genes.”
Carl Ernst, neuroscientist, The Neuro 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’s D2R, and an EU-JPRD grant funded in part by the Canadian Institutes of Health Research and the Fonds de recherche du Québec.
