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Experimental Therapy Crosses Blood-Brain Barrier To Treat Neurological Disease

The blood-brain barrier is a physiological blockade that alters the permeability of tiny blood vessels called capillaries in the brain. Its purpose is to protect the brain by preventing certain drugs, pathogens and other foreign substances from entering brain tissues. The barrier has also been a persistent roadblock to treating brain disease with drugs.

The scientists experimented with a set of derivative components of the fatty protein apoE, which binds to fat receptors on endothelial cells that form the inside surface of capillaries in the blood-brain barrier. They discovered that tagging some of the apoE components to the IDUA enzyme allowed the modified protein to attach to endothelial cells and cross through the cells to reach brain tissues.

Researchers injected experimental IDUAe1 into the tail veins of MPS I mouse models. The tests showed that – unlike currently available un-modified enzyme treatments – the modified enzyme penetrated the blood-brain barrier and entered brain neurons and astrocytes in a dose-dependent manner.

The researchers also reported that brain cells in the treated mice exhibited normalized levels of the glycosaminoglycans and the lysosomal enzyme b-hexosaminidase. With continued treatment through hematopoietic stem cell gene therapy, normalized levels persisted until the end of a five-month observation period, researchers said.

The scientists are continuing their preclinical studies to further verify the use of the experimental IDUA-based agents for treating MPS I, cautioning that results in laboratory mice may face additional challenges when translating to clinical application in humans. Researchers are also testing whether the large-molecule therapeutic procedure used in the current study can be leveraged to develop other neurotherapeutic agents that cross the blood-brain barrier.

Also collaborating on the study was Roscoe O. Brady, MD, a researcher and scientist emeritus at the National Institute of Neurological Disorders and Stroke.

Funding support for the study came from National Institutes of Health grants NS064330, DK074932 and U54 HL06-008.

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