A study has demonstrated that the Roche-designed Brain Shuttle technology efficiently transfers investigational antibodies from the blood through the blood-brain barrier (BBB) into the brain in preclinical models. Roche Pharma Early Research and Development scientists found that this transfer of antibodies through the BBB was associated with a marked improvement in amyloid reduction in the brain of a mouse model of Alzheimer’s disease.
Using protein engineering, scientists designed a system that exploits natural transport mechanisms to significantly increase the transfer of investigational antibodies into the brain in preclinical models, said Luca Santarelli, Head of Neuroscience, Ophthalmology and Rare Diseases at Roche pRED. “Using Roche’s Brain Shuttle technology, the target engagement of investigational antibodies in the brain in a preclinical model was increased by over 50-fold compared to the parent antibody.”
The BBB barrier imposes a major challenge to the development of therapies for neurological diseases, in particular large molecules, due to the limited ability with which they can penetrate through the BBB. The study published in Neuron showed that the Roche Brain Shuttle acts by engaging the natural transferrin receptor (TfR) in a specific mode that triggers a process called receptor-mediated transcytosis to transport molecules into the brain.