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“Brain Shuttle” Slips Alzheimer’s Antibodies into the Brain

Roche’s “Brain Shuttle” technology is helping antibodies fight Alzheimer’s. The body’s “Blood-Brain Barrier” blocks antibodies from getting to an Alzheimer’s brain. Learn how the Roche Brain Shuttle achieves a 50-fold increase in getting antibodies through to the brain.

The scientific journal Neuron 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 Early Research and Development (pRED) scientists found that such enhanced 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.

“Thanks to our sophisticated 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,” 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 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 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.

“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,” said Anirvan Ghosh, Head Neuroscience Discovery at Roche pRED.

“If we are able to clinically validate the preclinical results observed with the Brain Shuttle technology, it could lead us to a way to test investigational drugs in a variety of brain disorders,” said Per-Ola Freskgard, the Preclinical Project Leader for this technology platform at Roche pRED.


Roche, via Newswise.

Journal Reference:

  1. Jens Niewoehner, Bernd Bohrmann, Ludovic Collin, Eduard Urich, Hadassah Sade, Peter Maier, Petra Rueger, Jan Olaf Stracke, Wilma Lau, Alain C. Tissot, Hansruedi Loetscher, Anirvan Ghosh, Per-Ola Freskgård. Increased Brain Penetration and Potency of a Therapeutic Antibody Using a Monovalent Molecular Shuttle. Neuron, 2014; 81 (1): 49 DOI: 10.1016/j.neuron.2013.10.061
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July 13, 2014 6:29 pm

Do you have any on-going studies now?

Richard Taylor
Richard Taylor
July 17, 2014 4:23 am

Hello, more "if…then" results, which aren't really results, just reports. Everyone wants to have some "skin" in the alzheimer's cure game. Everyone touts their "skin" as a breakthrough, worthy of news conference announcements. Everyone wants everyone else to know, especially stock holders, that they are in the game. A real player.

Someone to whom others will come to if they ever prove andy molicule actually prevents/slows down any of the dementias. And if.elephants learn to fly.and then of course when they learn to fly we will need more and larger air ports, air planes, defense weapons against flying elephants, and the list of what we need to be working on right now, funding right now goes on and on. And so it goes with dementia research. Richard

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