Batten disease is a rare but fatal childhood neurodegenerative disorder, characterised by progressive cognitive decline, vision loss, seizures, and the accumulation of undegraded lysosomal material. There are currently no effective treatments, and drug delivery across the blood-brain barrier (BBB) remains a significant challenge in the development of therapies for central nervous system disorders.
To address this, we are using patient-derived induced pluripotent stem cells (iPSCs) to model key aspects of CLN3 Batten disease, including the generation of induced brain endothelial cells (iBECs) that closely mimic the human BBB. These iPSC-derived models provide a disease-relevant human platform to investigate cellular dysfunction, screen candidate compounds, and assess therapeutic delivery strategies.
One promising approach to overcome BBB-related drug delivery limitations is focused ultrasound (FUS), a non-invasive technique that can temporarily open the BBB to enhance access to the brain for therapeutic agents. In this study, we are investigating the effects of FUS on iPSC-derived iBECs from CLN3 patients to evaluate whether this method can safely and effectively modulate BBB permeability in the context of Batten disease.
We are also aiming to use previously selected drugs identified through computational drug repurposing to evaluate their potential therapeutic benefit. Together, the use of patient-specific iPSC models and FUS opens new avenues for targeted treatment strategies and personalised medicine in Batten disease and other childhood and adult dementias.
This presentation will highlight ongoing work to develop and refine these approaches, with the goal of improving drug delivery to the brain and accelerating translational research in neurodegenerative diseases.