Getting into the Brain

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Assistant Professor John Finke's research into Alzheimer's could change the way the disease is treated.

An estimated 5.4 million people in the United States are living with Alzheimer’s disease. By 2030 that number is expected to reach 8 million. At current rates, the number of Americans with Alzheimer’s will hit 16 million by mid-century.

Currently, only five drugs have been approved by the Federal Drug Administration to fight Alzheimer’s. These drugs manage symptoms but don’t stop the disease’s progression. More than 500 different drugs have been tested since 2002—only one received FDA approval. That’s a failure rate of 99.8%

These figures are worrisome but they also point to opportunity. “This is where academic science delivers,” says UW Tacoma Assistant Professor John Finke. “Businesses are pretty risk averse, they want to minimize risk. We are willing to beat our heads against a wall and every now and then the wall cracks and we get through.”Finke's work on protein folding led him to research Alzheimer's disease.

Finke hopes this is one of those times where academic science prevails. Funded by a National Institutes of Health grant, Finke is currently working on a way to get Alzheimer’s medications into the brain and keep them there. “I’m interested in looking at sugar groups and whether their presence can help drugs get into the brain better or prevent them from leaving,” he said.

The big problem with developing drugs to combat Alzheimer’s is something called the blood-brain barrier. The brain is a vulnerable organ; an infection here could result in serious illness or even death. For this reason, the brain is safeguarded by cells that actively regulate what goes in and out. “Think of these cells as a bunch of bricks stacked together and the gaps are filled in with mortar,” said Finke.

Getting past the blood-brain barrier is a critical component of Finke’s research. His work focuses on a type of sugar called sialic acid. Early experiments conducted in Finke’s lab have yielded promising results. “We tested antibodies side-by-side to see which one got in better and which one stayed in,” he said. “The antibody that had the sialic acid on it didn’t really affect the rate into the brain but it had a pretty major effect on getting out.”

In other words, antibodies (proteins in the body that fight disease) with sialic acid attached to them stayed in the brain at higher rates than antibodies that didn’t have sialic acid. This is significant because most medications that get past the blood-brain barrier only do so in small amounts and don’t stay very long. Getting more of a drug into the brain and getting more to stay could go a long way toward treating Alzheimer’s and other diseases where the brain has been damaged like Lupus, Multiple Sclerosis and Parkinson’s.

Finke’s work with sialic acid and antibodies produced an unexpected result. “The antibodies with sialic acid shut down the efflux system of antibodies lacking sialic acid, which is the brain’s process of pushing antibodies out,” he said. Exactly why this happened is unclear. More experiments are needed and Finke is currently working with mouse antibodies and cell models, not actual human brains.

Finke is committed to "green" science in his lab.  This approach produces less contamination than other methods.

Finke hopes to duplicate these results in human antibodies. Doing this requires building an infrastructure that will support conducting a large number of experiments. To achieve that, Finke recently received help from Browns Point residents Carl and Jan Fisher. The local couple donated funds that will allow Finke to purchase an automated plate system. “This piece of equipment allows you to take many different measurements at the same time,” said Finke.

Being able to do multiple experiments relatively quickly is important. “There’s a lot of variability in biology and you need to do a lot of different replicates in order to convince yourself that what you’re seeing is real,” said Finke.

In the long term, Finke hopes to grow cells in his lab that can be used to make replicates of the blood-brain barrier. This, combined with the automated plate system, will allow Finke to test hundreds, if not thousands of different scenarios. “We want to know what happens if we move the sialic acid to a different protein or what happens when we change the way the sialic acid is bound. There are 10,000 options and we’ve only explored one,” he said.

Finke’s project is a big undertaking; one he can’t do alone. Students help him run experiments, collect and sort through data. “It’s important to have an environment where students can try and fail and if they fail they just do it again and it’s not a big deal,” said Finke.

Growing up in the Burien area, Finke says research into Alzheimer’s and the blood-brain barrier mainly happened up north in Seattle. Times are changing and he sees UW Tacoma playing a vital role in developing academic science in the South Sound. “I see the campus performing a really important job and role in terms of exposing people in this area to the idea of science and what it can do,” he said.

Showing what science can do might include finding a way to treat Alzheimer’s. An answer to that problem, according to Finke, is behind a wall. “If we’re going to beat this disease or at least be able to treat it, we really have to think about the blood-brain barrier. It’s never going to happen until we get drugs in there.”

Written by: 
Eric Wilson-Edge / December 12, 2016
Media contact: 

John Burkhardt, UW Tacoma Communications, 253-692-4536 or