University of California, Davis collaboration
To explore the potential clinical implications, the Cincinnati team partnered with neurosurgery researchers at UC Davis.
Cameron Sadegh and Olga Chechneva co-led the UC Davis portion of the research. They induced hydrocephalus in adult animal models and then treated them with the experimental gene therapy developed by Luo’s team. It proved effective at preventing edema, or excess fluid, from entering brain tissue outside the ventricles.
“Hydrocephalus is a life-threatening condition, and our treatment options are surprisingly limited and outdated. Shunt treatment frequently fails, and alternative endoscopic treatments are not possible for many patients. We are eager to contribute to the preclinical development and safety testing of new, cell-targeted approaches to treat this devastating condition,” said Sadegh, a pediatric neurosurgeon-scientist and assistant professor in the UC Davis School of Medicine’s Department of Neurological Surgery.
“Showing that choroid plexus ablation reduces brain swelling does more than point to a new therapy. It sheds light on the mechanisms behind hydrocephalus and the brain injury it causes, knowledge that is critical for developing better treatments,” said Chechneva, a project scientist in Sadegh’s lab.
The Cincinnati team then validated the findings with a blinded analysis of the MRI data provided by the UC Davis team.
How does this build on previous research?
This research builds on prior Cincinnati research published in 2024, in which the Luo Lab was the first to directly ablate adult choroid plexus tissue, reducing CSF in adult animal models and marking a major breakthrough in the field.
What are areas for further study?
CSF is clearly critical, but its role in postnatal neurogenesis remains poorly understood. Because reducing CSF production is central to this therapy’s effectiveness, understanding any downstream effects on neurogenesis is an important next step.
Initial animal model testing shows that a loss of CSF production moderately reduces the ability of the brain to produce new neurons.
Despite concerns that reduced neurogenesis may affect the cellular networks underlying memory, the current state of hydrocephalus treatment leaves patients with a persistent, lifelong risk of repeated brain surgeries that can cumulatively diminish cognitive performance. So Luo and Taranov said further research, including a risk/benefit analysis, is needed.
Either way, Luo said the results are clear: Animal models that received the AAV gene therapy had much less fluid in their brain tissue.
What are the next steps?
Luo said further research will test the AAV gene therapy in larger animal models and human tissues. Ideally, that will be followed by human clinical trials. Ultimately, the goal is to develop an effective treatment for hydrocephalus.
“This is continuous work,” said Luo.
Luo and Taranov are both inventors on a pending patent related to this work.
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