Mass a unique molecular mechanism underlying the most prevalent types of acquired hydrocephalus has been identified by general researchers, potentially paving the way for the first nonsurgical treatment for the potentially fatal condition that affects about a million Americans.
According to research published in the journal Cell, the team discovered in animal models the mechanism by which an infection or bleed in the brain sets off a protracted neuroinflammatory response that boosts the choroid plexus tissue’s production of cerebrospinal fluid (CSF), causing the brain ventricles to swell.
“Finding a nonsurgical treatment for hydrocephalus, given the fact neurosurgery is fraught with tremendous morbidity and complications, has been the holy grail for our field,” says Kristopher Kahle, MD, PhD, a pediatric neurosurgeon at MGH and senior author of the study.
“We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. We’re hopeful these findings will pave the way for approval of an anti-inflammatory drug to treat hydrocephalus, which could be a game-changer for populations in the U.S. and around the world that don’t have access to surgery.”
Acquired hydrocephalus occurs in about one of every 500 births globally. Despite the fact that it can afflict anyone at any age, it is the most frequent reason for pediatric brain surgery. Children with hydrocephalus frequently die from the condition in undeveloped regions of the world where bacterial infection is the most common cause of the condition.
Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from hemorrhage in the brain. Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.
Bob Carter
In fact, brain surgery, which entails the insertion of a catheter-like shunt to drain fluid from the brain, is the only known treatment for acquired hydrocephalus. According to the Hydrocephalus Association, however, around half of all pediatric patient shunts fail two years after being implanted, necessitating repeated neurosurgical procedures and a lifetime of brain surgeries.
The MGH-led research team has made significant progress toward nonsurgical, pharmacologic treatment for humans by unraveling the special cellular and molecular biology that takes place within the brain following infection or severe bleeding.
The choroid plexus, a part of the brain that regularly pumps cerebrospinal fluid into the four ventricles of the brain to maintain the organ buoyant and safe inside the skull, is essential to the process.
The choroid plexus floods the brain ventricles with cerebral spinal fluid and immune cells from the periphery of the brain in a process known as a “cytokine storm,” or immune system overreaction, which is frequently seen in COVID-19 infections, swelling the brain ventricles in response to an infection or brain bleed, which can cause a dangerous neuroinflammatory response.
“Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from hemorrhage in the brain,” explains co-author Bob Carter, MD, PhD, chair of the Department of Neurosurgery at MGH.
“Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.”
MGH researchers are continuing to explore how rapamycin and other repurposed drugs, which quell the inflammation seen in acquired hydrocephalus, could be turned into an effective drug treatment for patients.
“What has me most excited is that this noninvasive therapy could provide a way to help young patients who don’t have access to neurosurgeons or shunts,” emphasizes Kahle. “No longer would a diagnosis of hydrocephalus be fatal for these children.”
Kahle is director of Pediatric Neurosurgery at MGH, and director of the Harvard Center for Hydrocephalus and Neurodevelopmental Disorders. Carter is chief of Neurosurgery Service at MGH and professor of Surgery at Harvard Medical School.
The National Institutes of Health and the Hydrocephalus Association funded the study.
