The journal Neuron has published results on the Roche-designed Brain Shuttle technology that efficiently transfers investigational antibodies from the blood through the blood-brain barrier (BBB) into the brain in preclinical models. Roche Pharma Research and Early Development (pRED) scientists have found that such enhanced transfer of antibodies through the BBB is associated with marked improvement in amyloid reduction in the brain of a mouse model of Alzheimer's disease.
“Using protein engineering we were able to design a system that exploits natural transport mechanisms to significantly increase the transfer of investigational antibodies into the brain in preclinical models,” says 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 is a selective interface that restricts movement of molecules between the bloodstream and central nervous system. This 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 it. The study shows 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.
“The efficacy of the Brain Shuttle technology in preclinical models suggests that this approach could deliver therapeutic molecules across the BBB. We will continue to investigate the potential of the Brain Shuttle technology to transport a variety of molecules such as growth factors, antibodies, peptides and oligonucleotides across the BBB,” says Anirvan Ghosh, Head, Neuroscience Discovery at Roche pRED. Read the article abstract.