Team Hydro focuses on supporting research that moves science towards a cure for Hydrocephalus, and we are happy to report that progress is being made!!! Having raised over $500,000 to date, Team Hydro currently supports a range of projects that are already working to make a cure for this difficult condition a reality!
“Cure-based research” sponsored by Team Hydro includes projects that seek to uncover the basic biology underlying this disease, determining and halting causative factors, and/or generating innovate new approaches to therapy.
Importantly, all our grantees are selected as a part of rigorous peer review process in conjunction with expert panels at the Hydrocephalus Association. Also, as we proudly state elsewhere, all Team Hydro fundraising dollars are applied directly into grant funding — not overhead costs.
A Few Projects Currently Underway w/ Team Hydro Sponsorship
A Molecular Shunt for Curing Hydrocephalus — Linninger Lab, University of Illinois
Hydrocephalus has multiple etiologies with a common symptom of water accumulation in the ventricles. The current treatment standard of fluid shunting via a ventricular catheter has remained largely unchanged over the past 50 years. Because water accumulation and fluid exchange within the brain are poorly understood, there is no cure for hydrocephalus. The astrocyte transmembrane protein, aquaporin-4, has been identified as a critical water transport channel. This project seeks to quantify amount and speed of water flux via AQP4 channels. We will use a novel microfluidic platform especially designed to mimic the in vivo morphology of astrocyte networks to study intracellular water transport. The new insights and data will create the foundation for managing and restoring cerebral water transport by pharmacological intervention. The envisioned pharmacological therapy would eliminate pathological water accumulation via molecular shunting, apt to cure hydrocephalus rather than merely treating its symptoms.
Goal: Develop an in vitro system that measures fluid dynamics and to test drugs that have the potential to improve fluid removal in hydrocephalus.
Therapeutic Modulation of Post-Hemorrhagic Hydrocephalus — McAllister Lab, Wash U.
Few attempts have been made to pharmacologically modulate the pathophysiology of hydrocephalus. However, we recently demonstrated that intraventricular infusions of “Decorin” significantly reduce neuroinflammation and prevent ventriculomegaly if given at the onset of hydrocephalus. Our collaborators have also developed a chemokine antibody that protects against demyelination4. These promising results require further study in a clinically relevant model of hydrocephalus. Neuroinflammatory processes are hallmarks of hydrocephalus5-9, and likely contribute to increases in brain stiffness observed clinically. Brain stiffness can be measured non-invasively with novel magnetic resonance elastography (MRE); this new technique will be used, in combination with other assessments of white matter integrity, cerebrospinal fluid (CSF) biomarkers, intracranial pressure (ICP), and cytopathology to identify specific drug targets and evaluate the effects of drug treatments. Our studies focus on post-hemorrhagic hydrocephalus (PHH) because of its prevalence. Our findings will lead to further development of treatments that could dramatically improve patient outcome.
Goal: Develop a higher model of post-hemorrhage hydrocephalus and determine the efficacy of one drug in stopping disease progression.
Analysis of the role of NFIX in the development of hydrocephalus — Piper Lab, University of Queensland
Our preliminary data have revealed a key role for the transcription factor NFIX in regulating the normal development of neural stem cells within the subventricular zone and of the ependymal cell layer of the lateral ventricles . Moreover, rodents  and humans  with reduced NFIX expression exhibit abnormal ventricular enlargement, implicating NFIX in the development of hydrocephalus. However, the processes underpinning this remain to be identified. Here we propose to use a suite of innovative techniques, coupled with an Nfix knockout mouse strain, to assess the cellular and molecular mechanisms by which NFIX mediates neural stem cell differentiation and subsequent ependymal cell development. Collectively this study will characterize the role of NFIX in the development of the ventricular system of the brain, and will provide crucial molecular insights into the formation of hydrocephalus, research that will provide the foundation towards developing strategies aimed at ameliorating this debilitating disorder
Preclinical Testing of TRPV4 Antagonists for the Treatment of Hydrocephalus — Blazer-Yost Lab, Indiana University – Purdue University Indianapolis
Our preliminary data indicate that TRPV4 antagonists ameliorate hydrocephalus in a rat model of Meckel Gruber Syndrome. The goals of the proposal are to: 1) determine if the efficacy is a class action of TRPV4 antagonists; 2) determine if TRPV4 antagonists are effective in another model of hydrocephalus representing a different species and different genetic mutation and; 3) use a continuous choroid plexus cell line to examine the effect of TPRV4 agonists and antagonists on transepithelial ion flux. Drug treatment will be followed with state-of-the-art rodent MRI for quantification of ventricular volumes. The cell line will be studied using well characterized electrophysiological techniques. If successful, these studies will form the framework for future pharmacokinetic and pharmacodynamic testing of TRPV4 antagonists, and structural/functional studies linking changes in brain metabolism with behavioral changes. The proposed studies will make a substantial contribution to progression toward developing the first drug treatment for hydrocephalus.
Goal: Prove the efficacy of a compound to ameliorate ventriculomegaly in multiple mouse models.
Past Projects w/ Team Hydro Sponsorship
Augurin as a novel choroid plexus-derived peptide hormone that regulates CSF formation by controlling epithelial cell homeostasis — Sonia Podvin and Andrew Baird, UCSD
The study hypothesized that the peptide hormone, augurin, is produced and secreted by the choroid plexus epithelium, is a ligand for an unknown receptor and has a critical function in CSF fluid homeostatsis. If proven, researchers predict that augurin can be manipulated pharmacologically to treat hydrocephalus.