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How anti-GRP78 antibodies could help therapeutic mAbs get through the BBB

Biogen Inc. has discovered antibodies in patients with a rare CNS autoimmune disease that could provide a new way to deliver mAbs across the blood-brain barrier, an application with wide-reaching ramifications for neurologic drug development.

The inability to concentrate therapeutic antibodies in the brain has long dogged drug makers, particularly in Alzheimer’s disease, where insufficient levels of anti-β amyloid antibodies is proposed as one cause of their failure to clear senile plaques.

Biogen’s Richard Ransohoff, a lead author on the study, told BioCentury that after IV administration only 1 out of 1,000 antibody molecules makes it across the barrier. “It would be valuable to be able to get those antibodies into the brain at higher levels,” and to get them in deeper, he said. Ransohoff is VP and Research Unit Head, Neuroimmunology, Acute Neurology and Pain.

Ransohoff said that other diseases in Biogen’s pipeline that may benefit from increased transit of mAbs into the brain include Parkinson’s disease, frontal temporal dementia and other tauopathies.

In studying the pathogenesis of neuromyelitis optica (NMO), his team and its academic collaborators identified two antibodies targeting the heat shock protein GRP78, and found the molecules specifically bind brain endothelial cells and make

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