A medication commonly prescribed for type 2 diabetes could offer a less invasive treatment option for patients with hydrocephalus, according to new research from Northwestern University published in the Journal of Clinical Investigation.
Hydrocephalus occurs when excess cerebrospinal fluid accumulates within the skull, causing pressure on the brain.
Normal pressure hydrocephalus (NPH) is a form of this condition often affecting older adults, with symptoms including cognitive impairment, difficulty walking and balance problems, and bladder dysfunction.
Around 3% of people aged over 65 are affected by this condition.
Currently, the main treatment for hydrocephalus involves surgically inserting a device called a ventriculoperitoneal shunt. This shunt drains excess fluid away from the brain to the abdomen, relieving symptoms and improving quality of life.
While effective, this procedure carries risks associated with any invasive surgery.
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“There’s currently no approved medication to treat hydrocephalus, making surgery the only viable option,” said senior author Dr Stephen Magill, Assistant Professor of Neurological Surgery at Northwestern University.
The discovery that diabetes medication could potentially manage hydrocephalus occurred after Dr Magill observed significant shrinkage in brain ventricles in a hydrocephalus patient who began treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors for their diabetes.
SGLT2 inhibitors are widely prescribed to manage blood sugar, improve heart and kidney function, and aid weight loss in type 2 diabetes.
Dr Magill explained, “SGLT2 inhibitors act primarily by blocking receptors in the kidneys to regulate blood sugar levels.
Interestingly, these same receptors are also present in a brain structure called the choroid plexus, responsible for producing cerebrospinal fluid. Although animal studies hinted at this connection, its clinical significance was previously not fully recognised.”
To further investigate this phenomenon, researchers reviewed CT scans of three hydrocephalus patients who underwent shunt surgery and subsequently began taking SGLT2 inhibitors for diabetes management. After starting the medication, each patient experienced a measurable decrease in ventricle size, with one patient even needing their shunt adjusted due to significant fluid reduction.
“This finding suggests a potential breakthrough, as these diabetes drugs might provide a non-surgical method to manage hydrocephalus,” Dr Magill added.
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The findings have inspired further research into SGLT2 inhibitors’ ability to prevent or treat hydrocephalus. Dr Magill’s team is now studying mouse models to better understand the precise impact of these drugs on cerebrospinal fluid dynamics.
This research could significantly advance treatment options not only for normal pressure hydrocephalus but also for hydrocephalus that occurs following traumatic brain injuries.
“Our discovery opens exciting new avenues for hydrocephalus treatment, potentially reducing the need for surgical intervention and associated risks,” said Dr Magill. “It also deepens our understanding of how these diabetes medications function beyond their original purpose.”
