Protein 'crossing guard' carries Alzheimer's drug past the blood-brain barrier

Combined proteins dissolve plaque in the brain as a potential treatment for Alzheimer's.--Courtesy of UPenn

To deliver large proteins past the blood-brain barrier for the treatment of Alzheimer's, researchers at the University of Pennsylvania have developed a compound that acts as a molecular "crossing guard" for drugs to safely target brain cells and clear plaques believed to cause symptoms of the disease.

Getting these large molecules past the brain's natural barrier is tricky and poses one of the difficult delivery problems for drugs designed to target the organ. And now, as published in the journal Molecular Therapy, the UPenn researchers coupled myelin basic protein (MBP)--known to break down the "plaque" amyloid beta--with another protein called cholera toxin B as a carrier.

To break down the plaque, MBP breaks down tangles in the amyloid beta, but first it needs to get there. The researchers fed healthy mice with genetically engineered capsules that resembled the coupled proteins and also carried a fluorescent tracker, which they then found had crossed into the brain and retina of the eye, according to the university.

"When we found the glowing protein in the brain and the retina we were quite thrilled," said lead researcher Henry Daniell in a statement. "If the protein could cross the barrier in healthy mice, we thought it was likely that it could cross in Alzheimer's patients' brains, because their barrier is somewhat impaired."

They then targeted the brains of mice with Alzheimer's, using another tracker that binds to plaques, and they found that plaques had dissolved by as much as 60% when exposed to the dual compound. The delivery method also worked for older mice as a preventive measure that reduced plaques by up to 70% in the hippocampus and up to 40% in the cortex.

"Really no one knows whether the memory problems [of] people who have Alzheimer's disease are due to the dementia or problems with their eyes," Daniell said. "Here we show it may be both, and that we can dissolve the plaques through an oral route."

- here's the UPenn report
- get the research abstract

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