How to Get Into the Brain

The human brain is one of the most complex systems in the known universe. Nearly 100 billion brain cells, called neurons, make over 500 trillion connections. Given its profound importance, you can imagine that our brains have some pretty serious security measures.

One of these security measures is the blood-brain barrier (BBB), a protective layer of cells that only allows certain molecules to pass through it from the blood into the brain itself. Other molecules, like most proteins and antibodies, can’t pass through.

The BBB is an important protective measure, but it also makes it very challenging to use biologic medicines for diseases of the brain, like Alzheimer’s disease. On top of that, our scientists have shown in preclinical models of Alzheimer’s disease that the BBB remains largely intact. This finding challenges a widely held belief that the BBB is compromised in Alzheimer’s disease, and that therapeutic antibodies can work themselves into the brain to treat the disease.

Ultimately, what we need are new ways to overcome this fundamental problem in antibody delivery to the brain.

We may have found one. Our scientists have developed a new type of bi-specific antibody that can “piggy-back” on an existing transportation system into the brain. One half of the antibody is designed to take advantage of the existing transport system, the other half is designed to target the abnormal amyloid plaques characteristic of Alzheimer’s disease.

To learn more about this new type of antibody that crosses the blood brain barrier, watch the video and read the papers from Genentech scientists below.


Learn More

Neuron. "Discovery of novel blood-brain barrier targets to enhance brain uptake of therapeutic antibodies."

Neuron. "Lack of Widespread BBB Disruption in Alzheimer’s Disease Models: Focus on Therapeutic Antibodies."

Journal of Experimental Medicine. “Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants.”

Science Translational Medicine. “Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the Blood-Brain Barrier.”

Science Translational Medicine. “Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target.”

Science Translational Medicine. “A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-β Production in Vivo.”