HMN 2025: How Diabetes drug might function different therapy possibility for hydrocephalus

A drug generally used to deal with sort 2 diabetes might cut back extra fluid within the brains of sufferers with hydrocephalus, which might assist deal with the illness much less invasively than present remedies, in line with a Northwestern Medicine study published within the Journal of Clinical Investigation.

Stephen Magill, MD, Ph.D., assistant professor of Neurological Surgery, was senior writer of the review.

Normal stress hydrocephalus happens when extra cerebrospinal fluid builds up contained in the cranium and places stress on the mind. The reason for the {condition} is elusive and impacts as much as 3% of people over the age of 65, with signs together with cognitive decline, issue strolling and bladder issues.

Patients are usually handled with everlasting ventriculoperitoneal shunts, that are surgically implanted within the entrance or again of the cranium and are related to a valve that diverts extra cerebrospinal fluid away from the mind and into the stomach where it’s absorbed. The process has been proven to dramatically enhance mobility, bladder {control} and cognitive functioning in sufferers with hydrocephalus, in line with Magill.

“It’s an important process as a result of it is one of many few issues you are able to do that really reverses these signs,” Magill mentioned.

There is, nonetheless, no pharmacological therapy at present authorised to deal with hydrocephalus. Additionally, almost 20% of sufferers with regular stress hydrocephalus even have sort 2 diabetes and take sodium/glucose cotransporter 2 (SGLT2) inhibitors to handle their blood sugar, cardiovascular and kidney perform, and weight reduction.

Magill lately noticed a discount within the mind ventricle dimension in a affected person with hydrocephalus who had a ventriculoperitoneal shunt surgically implanted after which started taking SGLT2 inhibitors to deal with their sort 2 diabetes. This phenomenon prompted Magill to additional examine the impression of SGLT2 inhibitors on ventricular dimension in sufferers with hydrocephalus.

“The medicine inhibits a receptor discovered within the kidneys, which is where it really works for diabetes. However, that receptor can be expressed within the choroid plexus, which is the construction within the mind that secretes the spinal fluid. Although this was recognized from animal research, the scientific features of this biology haven’t been totally appreciated,” Magill mentioned.

In the present study, three sufferers with hydrocephalus underwent CT scans each earlier than and after surgical procedure for ventriculoperitoneal shunts. After surgical procedure, every affected person started taking SGLT2 inhibitors for a medical indication after which underwent extra CT scans.

From analyzing these scans, Magill’s staff found that each one three sufferers confirmed a discount in ventricle dimension in addition to structural modifications of their brains after beginning SGLT2 remedy. One affected person demonstrated dramatic ventricle dimension discount resulting from ventricular collapse and required a shunt valve adjustment to scale back cerebrospinal fluid drainage.

“It’s a very attention-grabbing scientific remark as a result of it raises the likelihood that these medicines may very well be used to deal with regular stress hydrocephalus sooner or later, which might usually require surgical procedure,” Magill mentioned.

Magill mentioned the findings have sparked a brand new line of analysis in finding out how SGLT2 inhibitors might assist stop hydrocephalus, including that his staff is now finding out SGLT2 knockout mouse models to higher perceive the drug’s impression on ventricular dimension.

Their findings might in the end inform new therapeutic methods for treating regular stress hydrocephalus in addition to post-traumatic hydrocephalus, or the buildup of cerebrospinal fluid after traumatic mind harm, in line with Magill.

“This sparks a brand new line of analysis on how regular pressured hydrocephalus develops, what causes it, how this protein works in creating and secreting spinal fluid, and has direct translational implications,” Magill mentioned. “There’s an entire new avenue of probably treating this illness which may save a affected person from having surgical procedure, and there are at all times dangers with surgical procedure. It will even evolve our understanding of how these medicine work.”