Choroid Plexus Targeted NKCC1 Gene Therapy for the Treatment of Hydrocephalus
AAV-targeted augmentation of NKCC1 expression to reverse blood-induced ventriculomegaly and increased CSF clearance capacity
Background
A subset of infants and adults with hemorrhagic stroke and intraventricular hemorrhage (IVH) ultimately develop a life-threatening accumulation of cerebrospinal fluid (CSF), termed post-hemorrhagic hydrocephalus (PHH). An incomplete understanding of this variably progressing condition has hampered the development of new therapies outside of the current framework of serial neurosurgical interventions. There is a need for a new treatment of hydrocephalus that stems from a deeper, more comprehensive understanding of the condition.
Technology Overview
The researchers from Boston Children’s Hospital have discovered a therapeutically targetable choroid plexus (ChP) mechanism of CSF surveillance and potassium homeostasis that decreased ventricle size in embryonic, neonatal, and adult mouse models of IVH. They have invented a method to harness NKCC1 augmentation approaches for the treatment of hydrocephalus. The inventors’ data highlight a novel role of the ChP to rapidly compensate for alterations in CSF homeostasis following IVH and demonstrate the utility of targeted gene therapy to mitigate intracranial fluid imbalance following hemorrhages.
Further Details:
Benefits
- Adeno‑associated viral vector (AAV) targeted augmentation of NKCC1 expression rapidly reverses blood-induced ventriculomegaly and leads to persistently increased CSF clearance capacity, validating the model and treating the most salient clinical features of PHH
- Increased understanding of PHH
- Novel PHH therapy development
Applications
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Treatment of PHH
- Further research on PHH
