Hydrocephalus is a devasting disease for which there are no pharmaceutical treatments.

Currently the standard of care involves brain surgery—most usually the placement of a shunt to drain excess cerebrospinal fluid (CSF) from the brain to another area of the body. However, shunts routinely fail for a variety of reasons including infection, blockage and equipment malfunction predisposing the patient to multiple brain surgeries.

While pediatric hydrocephalus is perhaps the most recognizable form, there are multiple causes of this condition in older children and adults including traumatic brain injury, stroke, infection and genetic predisposition. Regardless of the precipitating factors, there is an excess of CSF in the brain and an enlargement of the cerebral ventricles.

It is our hypothesis that pharmaceuticals that could decrease CSF production on an as-needed basis would be helpful in treating most forms of hydrocephalus. Alternatively, pharmaceuticals that target aspects of the pathological changes such as inflammation and neuronal cell death would also be beneficial. Rational drug design for such potential treatments is based on a more detailed understanding of the production of CSF by the choroid plexus epithelium as well as the pathological changes that occur in response to the precipitating causes. The small tissue comprising the choroid plexus produces approximately 500 ml of CSF per day, the composition of which varies according to physiological, diurnal, and pathophysiological influences. The pathological changes likely include production of toxic intermediates, inflammation, changes in fluid electrolyte homeostasis, and ultimately, cell damage and death.