Penn scientists find protein to dissolve Alzheimer's plaque

Kathleen Blanchard's picture
A new future for Alzheimer's treatment?
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In the new study published in the journal Molecular Therapy, University of Pennsylvania researchers describe how they have found a way to penetrate the blood-brain barrier with a protein that dissolves tangles in the brain's of people with Alzheimer’s disease

One of the hurdles to treating the devastating neurological disease is the difficulty of finding compounds that can penetrate through the tightly packed cells of the central nervous system into the brain.

Untangling Alzheimer's plaques

The researchers have found a way to break the blood-brain barrier by teaming up two molecules – one that targets brain cells and another that dissolves Alzheimer’s plaques.

The team, led by Henry Daniell, a professor in Penn's School of Dental Medicine's departments of biochemistry and pathology and director of translational research used the protein cholera toxin B, or CTB that is both non-toxic and approved for use by the FDA for use in humans.

After identifying the protein, Daniell and his team then looked for another protein that would dissolve amyloid beta (Aβ) plaques that are in the brains of patients with Alzheimer’s and thought to be the cause of dementia – one that could target the tangles that form in the brain from Alzheimer’s disease.

"These tangles of beta amyloid are known to be the problem in Alzheimer's," says Daniell. "So our idea was to chop the protein back to their normal size so they wouldn't form these tangles."

How they did it

The researchers also knew myelin basic protein (MBP) that is important for proper nerve function has been shown to degrade Aβ chains in the brain.

When they fed mice a freeze dried CTB-MBP compound; then traced it by adding a fluorescent MBP carrier, they found it traveled to the brain in addition to the retina of the eye.

"When we found the glowing protein in the brain and the retina we were quite thrilled," said Daniell. "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."

When they removed the CBT “carrier” from the protein the compound no longer entered the brain and retina, which told the researchers CBT was an essential part of the delivery system.

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Next they gave the compound to mice bred to develop Alzheimer’s disease and followed the results using a “stain” to watch plaques in the brain dissolve.

For a follow-up, and in conjunctions with the National Institutes of Health, they performed the same tests on the brains of people who had died from Alzheimer’s disease; using the same type of staining technique.

Lastly, they administered oral capsules containing CTB-MBP to “old” Alzheimer’s bred mice. They found a 70 percent reduction in Alzheimer’s plaques in one area of the brain and a 50 percent reduction in another after three months.

Alzheimer’s disease patients also have plaque in the retina. In the study, mice given the protein compound were also free of retinal plaque after being given the compound.

Is Alzheimer’s a brain or an eye disease?

Two highlights of the researcher’s work is that no one knows if Alzheimer’s memory problems are the result of dementia or eye problems, Daniell said. The compound dissolved both, which addresses both possibilities.

Another is that they treated the mice using a compound that can be taken orally.

What next?

The next step is to find out if dissolving Alzheimer’s plaques with the protein combination changes the behavior of mice with the disease and improves memory.

The researchers also hope the technique could lead to new drugs that can penetrate the blood brain barrier to treat Alzheimer’s and other neurological diseases.

Molecular Therapy
6 December 2013
doi:10.1038/mt.2013.273

Image credit:
Wikimedia Commons

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7 new guidelines for Alzheimer's prevention
Why zinc could prevent Alzheimer's disease
The Alzheimer's smell test

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Comments

so if you can dissolve Alzheimer's plaque in the brain could this also help people with cerebral Amyloid angiopathy.