How to Overcome the Blood-Brain Barrier to Deliver New Medicines

The brain’s protection barrier prevents medicines from getting in, but new approaches are finding ways to bust through and treat central nervous system diseases.

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The same structure in the brain that offers protection and transports nutrients and other essential substances also makes it virtually impossible for medicines to enter and reach their intended targets in the brain. 

The blood-brain barrier (BBB) is a complex and intricate system of cells that come together around the blood vessels in the brain. It maintains proper function of the brain, but it also makes it harder to discover and develop new medicines to treat diseases of the brain, such as Alzheimer’s disease, Parkinson’s and others. 

“Fewer than 5 percent of small-molecule medicines and virtually no biologic medicines are able to penetrate the blood-brain barrier,” says Alfred Hahn, Ph.D., senior director and head of discovery at AbbVie’s R&D center in Ludwigshafen, Germany. “These numbers do not deter us; we believe we’re onto a number of promising new approaches that may allow us to improve these odds.”
 

Unmet need drives new approaches

Over the past several decades, significant strides have been made in discovering and developing new medicines for a wide range of conditions, from heart-related diseases and viral infections to certain types of cancer. 

The same cannot be said for diseases of the central nervous system (CNS), where significant need for new treatments remains. 

Nearly 47 million people are living with dementia1 and there are millions of other people who have Parkinson’s disease, multiple sclerosis and other CNS diseases.2 A number of potential approaches are emerging for finding new ways to cross the BBB without disrupting the brain’s functioning. Here are three of them:

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Bispecifics combine two antibodies that can bind to two different targets.

1. The bispecific approach

Researchers are exploring the use of bispecific antibodies. Unlike a single antibody, which binds to one target, dual-variable domain immunoglobulins, or DVDs, combine two antibodies, which have the capabilities to bind to two separate targets.

The BBB contains many transport pathways, and bispecifics could take advantage. 


“Targeted DVDs may prove useful in delivering drugs across the blood-brain barrier because one of the antibodies could target a receptor that regulates transport into the brain, while the other antibody could serve as the therapeutic payload, delivering the medicine to the site of disease,” says Andy Goodearl, Ph.D., director of biologics research at the AbbVie Bioresearch Center in Worcester, Massachusetts, U.S.A.
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Nanotechnology has many potential applications in medical research.

2. Nanoparticles are like taxi cabs

Anamarija Curic, Ph.D., senior research scientist in the chemical entity formulation group in AbbVie Germany, is part of a team exploring the use of nanoparticles in new methods of drug delivery.

Nanoparticles are tiny particles that can’t be seen under a standard light microscope. For an idea of size, the particles measure 1 to 100 nanometers. For comparison, a single bacterium measures approximately 1,000 nanometers, while a tennis ball is 100 million nanometers.

The role of nanoparticles is to transport, something scientists are trying to put to use in drug research.

“Think of nanoparticles like taxi cabs with GPS on the surface, driving their passenger, a therapeutic medicine, directly into the brain,” Curic explains. “Our mission is to develop nanoparticles that could carry small molecules or biologics as their passengers, with controlled release in the diseased tissue.”

The promise of this approach has attracted the interest of companies and academic centers. AbbVie leads the BBB work stream of a large public-private partnership known as COMPACT, part of the Innovative Medicines Initiative (IMI). Nanotechnology is one key area of research being explored through this collaboration.
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Particles discharging from a cell as seen through an electron microscope.

3. Capsule packages

In another novel approach, scientists are using protein capsules to package drug molecules into tiny, micro-containers and take them across the BBB into the central nervous system. 

These tiny packages can be thought of like a “Trojan horse” – carrying something into the brain that previously was unable to pass through on its own, and bringing it straight to the diseased tissue. 

This direct targeting of the medicine also allows for smaller doses to be given to patients. AbbVie is exploring this exciting area of technology through a project co-funded by a grant from the Germany Ministry for Education and Research and in collaboration with another biotech company. 

“Given the number of different disease targets in the brain, it’s clear that a one-size-fits-all approach is not going to work,” Hahn says. “Pursuing a number of innovative new approaches to crossing the BBB gives us the best chance for being successful in helping patients.”

1 https://alz.org/global/
2 https://www.mstrust.org.uk/a-z/prevalence-and-incidence-multiple-sclerosis
 

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Jaquelin Finley
Email: jaquelin.finley@abbvie.com
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