Across the Great Divide: Getting Antibodies into the Brain

Lundbeck and the Wyss Institute for Biologically Inspired Engineering at Harvard University are collaborating to research new ways to deliver antibodies across the blood-brain barrier.

The blood-brain barrier is a fortress-like network of blood vessels surrounding the brain that keeps unwanted substances out.¹ Normally, this barrier serves as vital protection against toxins, infections and other threats. But when treating brain diseases, the blood-brain barrier makes it more difficult to get drugs into the brain, where they could have a therapeutic effect.

The barrier poses a particular challenge for treatments based on monoclonal antibodies (mABs), larger molecules that are a mainstay of treating diseases in other parts of the body, including many cancers and autoimmune disorders. Due to their large size, only a small percentage of a given mAB dose will penetrate the blood-brain barrier, meaning extremely high doses are typically necessary to achieve a therapeutic level. This high dose level can make it more difficult to develop safe and effective mAB treatments for brain diseases. ²

The Wyss Institute’s artificial blood-brain-barrier
Currently, researchers studying whether and how drugs in development enter the brain must rely on testing in mice and non-human primates. However, this can pose challenges because the blood-brain barrier of mice and non-human primates differs from that of humans. The recently announced collaboration between Lundbeck and the Wyss Institute will research delivery methods employing the institute’s Human Blood-Brain Barrier Chip technology, an artificial blood-brain barrier created from differentiated human stem cells that can be manipulated and studied to a greater extent.²

The Lundbeck-Wyss Institute collaboration aims to identify new molecules in the human blood-brain barrier that could be targeted and engaged to more effectively shuttle drugs into the brain. The research could contribute to the understanding and discovery of the fundamental rules of how to design antibodies so that they can efficiently cross the blood-brain barrier; and it may speed up the research process and potentially lead to new treatments.

“The blood-brain barrier is always a challenge when working with brain diseases. If we cannot get the medicines into the brain, there will of course be no effect,” says Allan Jensen, Lundbeck’s vice president of Biotherapeutic Discovery. “This artificial blood-brain barrier may allow us to jump several steps ahead in all of our antibody discovery projects, increasing our knowledge while reducing risk.”

Lundbeck is a longtime innovator in brain research, and the new collaboration is part of the company’s increased focus on therapeutic antibodies for brain diseases. Recently, Lundbeck had its first antibody migraine preventive treatment approved in the United States. And the company’s pipeline includes several development projects focusing on antibodies to treat complex brain diseases like Parkinson’s disease.

Sources
1. Blood-Brain Barrier. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/blood-brain-barrier Accessed 7/13/2020.

2. Brain Targeting Program: Shuttles for Brain Delivery of Therapeutics and Diagnostics. The Wyss Institute for Biologically Inspired Engineering at Harvard University. https://wyss.harvard.edu/technology/brain-targeting-program-shuttles-for-brain-delivery-of-therapeutics-and-diagnostics/. Accessed 7/13/2020.