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Notice of Special Interest: Disease Mechanisms of Prenatal and Pediatric Hydrocephalus

National Institutes of Health

The purpose of this Notice is to inform potential applicants about an area of special interest to NINDS in hypothesis-driven research projects that focus on deciphering the molecular, cellular and developmental mechanisms involved in the pathogenesis of prenatal and/or pediatric hydrocephalus and to examine new approaches for treatment.

Hydrocephalus is a condition in which the primary characteristic is excessive accumulation of cerebrospinal fluid (CSF) in the brain resulting in enlargement of the ventricles. Prenatal and/or pediatric hydrocephalus may be caused by either intrinsic factors including genetics or extrinsic factors including hemorrhage or infections. It occurs in 1 in 1000 newborns. The most common treatment for hydrocephalus is surgical drainage by the placement of a shunt or endoscopic third ventriculostomy with choroid plexus cauterization (ETV-CPC). Little is known about the pathogenesis (biological mechanisms leading to the disease state) of prenatal and/or pediatric hydrocephalus.

There have been recent advances in understanding the etiology of prenatal and pediatric hydrocephalus including investigations into the role of neural progenitor cells, cilia and genetics. Despite these advances, there are still significant gaps in our understanding the molecular, cellular and developmental mechanisms involved in the pathogenesis of hydrocephalus.

This Notice invites hypothesis-driven research projects that focus on deciphering the molecular, cellular and developmental mechanisms involved in the pathogenesis of prenatal and/or pediatric hydrocephalus. A greater understanding of the disease mechanisms of prenatal and/or pediatric hydrocephalus is critical for the establishment of preventative measures and new therapeutics. Topics of interest include 1) understanding the pathogenesis of prenatal and/or pediatric hydrocephalus due to intrinsic factors including genetic factors; and 2) understanding the pathogenesis of prenatal and/or pediatric hydrocephalus due to extrinsic factors including hemorrhage and infection.

For PA-20-183 , only mechanistic clinical trials will be accepted in accordance with NOT-NS-18-011 . NIH defines a mechanistic clinical trial as follows: "A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention.”

Studies that focus on the following will be considered non-responsive: research related to acquired hydrocephalus in adults (e.g., due to brain tumor, traumatic brain injury and hemorrhage); research related to normal pressure hydrocephalus; pediatric research not focused on hydrocephalus pathogenesis but on perinatal traumatic brain injury, brain hemorrhage and hypoxia; shunt development; natural history studies; and non-mechanistic clinical trials (i.e., efficacy, effectiveness, and implementation).

Research that proposes to develop or substantially modify existing cutting-edge technologies that will advance prenatal and/or pediatric hydrocephalus research is being supported by NOT-NS-23-003 .

This notice applies to application receipt dates on or after October 5, 2022 and subsequent receipt dates through December 10, 2025.

NOT-NS-23-004