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Fish Without Jaws Bite The Blood-Brain Barrier

A major challenge in the treatment of cancers and other brain disorders is to ensure that medicines reach their goals. A team of biomedical engineers and clinical scientists from the University of Wisconsin-Madison and the University of Texas at Austin borrowed molecules from the parasite immune system of the sea lamprey to deliver cancer drugs directly to brain tumors.

They published their results today (May 15, 2019) in the journal Science Advances.

Unlike most medications currently used, which address specific characteristics in or within the individual cells of the organs and tissues of our body, the molecules derived from the lamprey point to a different target: the extracellular matrix, a tangled mesh of proteins and sugars that supports and surrounds all the cells in the brain.

The researchers believe that the molecules could be adapted and combined with a wide range of other therapies, offering the hope of treating numerous brain ailments beyond tumors, such as multiple sclerosis, Alzheimer's disease or even traumatic injuries.

"This set of targeted molecules seems a bit agnostic to the disease," says Eric Shusta, professor of chemical and biological engineering at UW-Madison. "We believe it could be applied as a platform technology in multiple conditions."

Technology takes advantage of the fact that many diseases disrupt one of the body's natural defense mechanisms: the blood-brain barrier, which lines the blood vessels of the central nervous system and protects the brain from potential threats, such as toxins or pathogens in circulation.

Many drugs, including molecules derived from lamprey, cannot reach targets in the brain when they are injected into the bloodstream, because the blood-brain barrier usually prevents large molecules from leaving the blood vessels in the brain.

However, in conditions such as brain cancer, stroke, trauma and multiple sclerosis, the barrier becomes permeable in and around the locations of the disease. A dripping barrier offers a unique entry point. It will allow lamprey molecules that are directed to the matrix to access the brain and deliver drugs precisely to the target.

"Molecules like this usually cannot carry the load to the brain, but wherever there is an interruption of the blood-brain barrier, they can deliver drugs directly to the site of the pathology," says Shusta.

Knowing that brain tumors often cause the barrier to escape, the researchers linked the lamprey-derived molecules to a chemotherapy approved by the Food and Drug Administration called doxorubicin. The treatment prolonged survival in mouse models of glioblastoma, the incurable brain cancer that affected Senators John McCain and Ted Kennedy.

By: Preeti Narula