Can ultrasound be used to fight Alzheimer’s?

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• Amna Nawaz:

  Nearly six million people in this country have Alzheimer's disease. Tragically, no treatment can fully stop it yet.

  But researchers around the world are trying to crack the complicated puzzle that is Alzheimer's.

  Tonight, Miles O'Brien reports on intriguing research and a different approach to battling the disease.

  For the record, some of that work is funded by retired Senator Jay Rockefeller. His wife, Sharon, is the CEO of WETA, which owns the "NewsHour."

  This story is part of our regular look at the Leading Edge of science.

• Judi Polak:

  Hello, everybody.

• Miles O’Brien:

  To know Judi Polak is to love her.

• Judi Polak:

  I miss you guys.

• Woman:

  We miss you too, Judi.

• Miles O’Brien:

  She brims with energy, kindness and humor.

• Judi Polak:

  Did I tell you about that? Can you believe that?

• Woman:

  I know.

• Miles O’Brien:

  At first, you would never know.

• Judi Polak:

  I mean, I can't remember what I did yesterday, but I can remember Stacy Elsa from 30 years ago.

• Miles O’Brien:

  But, eventually, her disease reveals what it is stealing, her memory.

• Judi Polak:

  Do I have my keys? Of course, this is the day I can't find it.

  Hello.

• Miles O’Brien:

  At age 61, Judi Polak is now five years into her new normal after a bleak diagnosis. She has Alzheimer's disease.

• Judi Polak:

  I would go to say something, and it just didn't come out, probably just like I'm talking now. It's very difficult to have a fluent conversation.

• Miles O’Brien:

  She was a neonatal nurse practitioner with a doctoral degree. Husband Mark is a neonatologist.

  So they dove into this case, the one that came home, with a lot of professional insight, along with the personal anguish.

• Mark Polak:

  We need to fight this. She's not going to sit here in a chair and slowly deteriorate. One of our good friends said, the first person to be cured with Alzheimer's is alive today. And that became my morning and evening prayer.

• Miles O’Brien:

  That conviction is what brought them to this moment on October 16, 2018. The place is J.W. Ruby Memorial Hospital in Morgantown, West Virginia, the hub of their professional lives for decades.

  But, on this day, the gurney was turned, and patient Judi Polak made some medical history in a clinical trial. A team of scientists, engineers and practitioners deployed a novel device to take aim at a big barrier to progress in the fight against Alzheimer's the blood-brain barrier.

  It is a semi permeable sheathing around blood vessels in the brain that repels harmful germs, while allowing essential nutrients in. The problem is, the barrier also prevents most medications from getting through because of their larger molecular size.

• Ali Rezai:

  If you can open up the blood-brain barrier, you have entry into the brain for the targeted delivery of medications.

• Miles O’Brien:

  Neuroscientist Ali Rezai is executive chair of the Rockefeller Neuroscience Institute at West Virginia University.

  Dr. Rezai is leading a team intent on breaking through Judi's blood-brain barrier safely and reversibly.

• Ali Rezai:

  Now you can deliver much less doses, which improves the safety profile, and you can deliver it more targeted to the area it needs to go to.

• Miles O’Brien:

  To temporarily open the barrier, they are using a combination of MRI and PET scans, an injection of tiny microbubbles, and a million-dollar helmet that sends out precisely focused beams of acoustic waves, ultrasound.

  Using the imagery, thousands of ultrasound waves are aimed at the hippocampus, the brain's memory center. The ultrasound vibrates the bubbles in the bloodstream, and they breach the barrier. It is a first. And it worked.

  By injecting a contrast agent, they can see the proof in MRI imaging.

• Ali Rezai:

  Contrast agent doesn't normally cross the blood-brain barrier, but here, this light area shows the opening of the blood-brain barrier in the hippocampus.

• Miles O’Brien:

  And, crucially, an MRI taken 24 hours later shows Judi's protective blood-brain barrier is once again closed.

• Ali Rezai:

  You don't want it open all the time. That will lead to a lot of problems.

• Miles O’Brien:

  Temporarily opening the blood-brain barrier may be a more effective means to get drugs where they are needed in the brain.

  But, for Alzheimer's, there are no effective drugs, despite more than 700 clinical trials.

• David Knopman:

  These drugs made people — at least some of them, so far, have actually made people worse.

• Miles O’Brien:

  Neurologist David Knopman is associate director of the Alzheimer's Disease Research Center at the Mayo Clinic in Rochester, Minnesota.

• David Knopman:

  It's extremely disheartening to have to sit in front of people, like I did earlier today, to say, I'm sorry, we haven't had any success.

• Miles O’Brien:

  Researchers believe two proteins, beta amyloid and tau, are the likely causes of Alzheimer's. In the brains of those afflicted, abnormal tau accumulates, creating so-called tangles inside neurons. In between the neurons, beta amyloid forms in clumps, so-called plaques.

  For many years, Alzheimer's researchers were focused on those amyloid plaques.

• David Knopman:

  We definitely need to look beyond amyloid. We need to be doing more of these phase one trials, looking at different targets. We need to take 99 shots on, 100 shots on goal to find one that's good, I'm fine with that.

• Miles O’Brien:

  But what if drugs weren't required to begin the fight against Alzheimer's? Researchers have found focused ultrasound alone can clear away plaques in mice. Early data suggests the technique may be doing the same for Judi and two others.

• Ali Rezai:

  This area had a decrease in plaques as compared to this area, which we didn't treat.

• Miles O’Brien:

  It's unclear why this happens. The ultrasound might trigger an immune response, or the brain's glymphatic system, which clears out waste. Regardless, in the case of the mice, their behavior and memory function improved.

• Ali Rezai:

  Hopefully, we can get replication of the animal studies that shows that the plaques were cleared and the symptoms improved over time.

• Miles O’Brien:

  It's possible mice may not be a good model for humans in this case. After all, nearly all those failed trials began with promising results in the animals.

  But after three ultrasound treatments, Judi and Mark are convinced she is doing better.

• Judi Polak:

  I feel that I have more cognitive awareness. I can't tell from right now what I'm doing, but I'm better than I was before.

• Miles O’Brien:

  To try and separate the data from the hope, the team at the Rockefeller Neuroscience Institute is subjecting Judi to some objective memory testing.

• Man:

  Car, brown, tree, bed, shirt.

• Marc Haut:

  Go ahead, tell me what you remember.

• Judi Polak:

  Car, bed. I was thinking about listening to it, and then I lost my — car — I lost — I don't know.

• Miles O’Brien:

  Neuropsychologist Marc Haut says it is too early to say if Judi's symptoms have improved.

• Marc Haut:

  It's hard to tell what's true change and what's just fluctuation. So, even your memory is better some days than others. Mine clearly is. And Judi is going to be even more affected by just daily variations.

• Miles O’Brien:

  None of this seems to slow Judi down. She is determined to power through, to stay in the game, as much as the disease allows. She still drives herself to a few destinations, to the gym for regular workouts.

• Judi Polak:

  Oh, right on my finger again. I am not very good at this.

• Miles O’Brien:

  And to her mother's house for a game of Yahtzee.

• Woman:

  Uh-oh.

  She is doing better. I can tell the difference. I used to have to show her everything.

• Miles O’Brien:

  She still goes to the neonatal intensive care unit to share lunch and love with her old colleagues and lifelong friends.

  And while she is there, she volunteers her time as a cuddler for premature babies.

• Judi Polak:

  This is what keeps me going.

  Hi, little one. Look at you. You're all dressed up. You have the hiccups.

• Miles O’Brien:

  This is what helps her fight the sadness and the boredom that comes with this relentless, cruel disease. But the stark reality tugs hard.

• Judi Polak:

  I'm fine when I'm at home, fine doing what I do, my daily routine. But this is going to get worse. I mean, it's going to happen.

• Mark Polak:

  I think there are still a lot of tangles, but I have to believe that there's a slight improvement, which, for me, is a victory. If we get an hour more of her, that's been well worth it.

• Miles O’Brien:

  Judi Polak is courageously fighting to make and keep her memories. And maybe, just maybe, it might lead to a memorable impact on a dreadful disease.

  For the "PBS NewsHour" I'm Miles O'Brien in Morgantown, West Virginia.