Andrew Hale, M.D., Ph.D., a neurosurgical resident in the University of Alabama at Birmingham Department of Neurosurgery, is the first author of a newly published paper in Science Translational Medicine. The paper defines the “Molecular Hallmarks of Hydrocephalus,” a condition that affects millions worldwide and is the leading reason for childhood brain surgery.

Hydrocephalus (HC) occurs as a result of dysregulated brain and cerebrospinal fluid (CSF) homeostasis, which often leads to CSF build up in the brain’s ventricles, causing pressure that can damage brain tissue.

While surgery is currently the only treatment option, high failure rates and repeated operations remain common.

The paper explains how efforts to understand fundamental molecular mechanisms may lead to development of pharmaceutical therapies that could alleviate morbidity and mortality associated with HC.

The paper summarizes the key molecular and cellular drivers of HC, including genetic risk factors, dysfunction in neural stem cells, abnormal brain development and disruptions in CSF flow. These insights offer a critical framework for understanding how hydrocephalus affects brain growth and structure.

The paper encourages the use of human-derived brain organoid models to simulate and study HC in ways that more accurately reflect human biology and suggests that this model is important for identifying new drug targets.

This work brings clarity to the complex biology of hydrocephalus and maps out the next steps for developing more effective treatments.