Morgantown residents participate in WVU clinical trial for Alzheimer’s.


Judi and Mark Polak like to stand in the spot where they first saw each other, steps away from what’s now Mark’s office at the West Virginia University Health Sciences Center. When they met, “Judi was a new nurse,” Mark remembers, “and I was a green medical student” at WVU.

They’ve been married now for 37 years. Mark is Health Sciences Center (HSC) chief of neonatology. And Judi had a career she loved at the HSC as a neonatal nurse practitioner and doctor of nursing practice—until she retired in 2015 after receiving a diagnosis of Alzheimer’s disease.

Now in her early 60s, she’s still in Alzheimer’s early stages, with only short-term memory loss.

Mark and Judi have always been caregivers. They cared for Judi’s father and Mark’s mother, both of whom faced memory issues. They care for Judi’s sister, diagnosed eight years ago with a glioblastoma, an aggressive brain tumor.

Given Judi’s professional and family caregiving stressors, she and Mark attributed her early Alzheimer’s symptoms to depression. “Some people burn the candle at both ends. She started a fire in the middle, too,” Mark says, his voice breaking.

Neither conceals their feelings about Judi’s diagnosis. Mark pushes verbally through emotion. He talks with vigor and passion. Judi smiles quickly when overcome, delicately turning her face away.

She’s much quieter but, when she responds, it’s with swift engagement.

“Forgetfulness” was the first sign of trouble, she says. “Not remembering my large cache of …”

“Knowledge?” suggests Mark.

“Passwords,” says Judi wryly. “I had to write everything down. I’m a writer-downer anyway, but I forgot a lot.”

Navigating the hospital’s electronic health records became difficult, so she consulted psychiatrist Marc Haut. In January 2014, Mark and Judi assembled with their family in Haut’s office, viewed Judi’s brain scan, and received the Alzheimer’s diagnosis. Mark was not prepared for the news. But, says Judi, “I was. Yup. I was.”

Judi and Mark weathered the shock together. “After we got through the boo-hooing,” Mark remembers, “it was like, ‘Well, we need to do something about this. We just can’t sit around and watch things float away.’”

Do something, they did. In September 2018, Judi became the first human to have the blood-brain barrier to her hippocampus—the part of the brain in charge of memories—opened via ultrasound as part of a potentially groundbreaking phase 2 clinical trial at WVU.

While Judi and Mark searched for a response, neurosurgeon Ali Rezai was engineering ambitious expansions at the Rockefeller Neuroscience Institute (RNI), established at WVU in 1999 to pioneer advances in brain health. Since taking the reins there in 2017, Rezai has been recruiting people from all over the country and outside the United States to come to Morgantown, he says, “people with backgrounds in data analytics, population health, machine learning, circadian rhythms, biology, neuromodulation. We recruited nearly 50 individuals in the past year to come here.”

The institute has also formed corporate partnerships. With Swiss company MindMaze, for example, Rezai’s team is exploring cognitive enhancement for Alzheimer’s using virtual reality.

Under Rezai’s direction, the institute partnered with Israeli company INSIGHTEC, which developed the ultrasound device Judi’s clinical trial is now testing. INSIGHTEC opted to host the treatment’s phase 2 trial—the second of a clinical trial’s potential four phases evaluates both safety and benefits—at WVU due, Rezai believes, to the institute’s ability to “rapidly initiate” the trial.

The process was very competitive. “We’re thrilled to be selected,” Rezai says. “Here locally in Morgantown is where new discoveries are happening.” Last year, for example, the institute was the first U.S. site to conduct a trial on a micropellet injected into the back to treat chronic sciatica pain locally, at the nerve, without opioids. Right now, it’s the world’s first site to do what Rezai describes as “a deep-brain stimulation trial, a brain pacemaker trial, for severe opioid addiction.”

The INSIGHTEC trial Judi is involved in builds on years of preclinical research into animal models of Alzheimer’s. While there are several kinds of dementia—some more treatable than Alzheimer’s, making early diagnosis essential—Alzheimer’s is distinguished by the presence of beta-amyloid plaques, or clumps of protein, in the brain. When researchers coaxed open the vascular filtration system known as the blood–brain barrier in animal brains using ultrasound, “these clumps of protein were significantly cleared, and memory and cognitive function in these animals improved. That’s what led to the FDA saying, ‘Okay, let’s explore this in patients,’” Rezai says of the U.S. Food and Drug Administration’s approval of testing on humans.

The blood-brain barrier is a dense network of blood vessels that is highly selective in what it allows into and out of the brain. Chemotherapy medications, antibiotics, and antibodies often can’t reach the brain, or only get through in diminished quantities, posing a major treatment challenge.

However, when microbubbles are injected into the body and reach the barrier, focused ultrasound waves can oscillate the bubbles, nudging open the tight junctions between the cells for about 24 hours.

“The theory,” Rezai says, “is that opening up the barrier modulates the immune system to accelerate the clearing of the brain plaques. It may also facilitate the clearance mechanism for removal of the accumulated protein in the brain.”

“The real breakthrough came when INSIGHTEC figured out how to focus the ultrasound inside the skull, because the skull really creates a problem for ultrasound,” explains WVU interventional neuroradiologist Jeffrey Carpenter. “It’s almost like having your surround sound system in rooms outside of where you are. The tuning of the surround sound is a little harder when you’re outside the bone. INSIGHTEC figured out how to do that.”

There’s no surgery involved: The three subjects in WVU’s trial remained awake and talking—in Judi’s case, Rezai recalls, “joking around”—during the three biweekly sets of ultrasound procedures they each underwent. It’s still too early to speak to any possible reduction in brain plaques or cognitive decline in the participants, but Rezai can say that the safety profile, his first priority, “was excellent, no problems” for all three patients. Risks such as swelling or bleeding in the brain have not occurred.

INSIGHTEC’s technology excites Carpenter, but he’s just as enthusiastic about what this trial and similar initiatives mean for health care in Morgantown and West Virginia. “Dr. Rezai brought in a lot of connections,” he says. “We’re going to have access to really, really smart clinicians: neurologists that really specialize in Alzheimer’s disease and are on the forefronts of their games. This is going to be a very exciting place for neurologists and neuroscientists to come and practice.”

An influx of specialists matters for Morgantown, because Alzheimer’s poses acute problems for West Virginia. The biggest predictor of Alzheimer’s is age, and West Virginia hovers among the three U.S. states with the highest percentages of seniors. The Chicago, Illinois–based Alzheimer’s Association reports that 38,000 West Virginians currently have Alzheimer’s—and the disease may be underdiagnosed. That 38,000 is expected to increase 16 percent by 2025. West Virginia’s Medicaid bill for Alzheimer’s is $430 million per year now, and that’s projected to increase 20 percent over the same period.

Not only are there many older residents in West Virginia, but the dementia risk for baby boomers, who shoulder much of the current caregiving burden, is increasing with their age. Many caring for elderly loved ones also care for children or grandchildren. Yet, says Sharon Rotenberry, executive director of the Alzheimer Association’s West Virginia chapter, “we cannot afford for these caregivers to stop doing what they do. We don’t have places for people to go if our caregivers aren’t doing what they’re doing.” Costs rise here, too: The state’s 106,000 unpaid caregivers have seen their own health care costs go up by $90 million after assuming their roles.

No one denies the urgency of Alzheimer’s for West Virginia, even in politics. On Capitol Hill, says Rotenberry, “every piece of legislation that involves this disease and treatment is cosponsored by Senator Shelley Moore Capito. And our congressmen vote for it. They vote for continued funding to the National Institutes of Health, all five of them. They voted for the BOLD Infrastructure for Alzheimer’s Act that passed last year, and that’s to better man public health.”

Capito agrees: When it comes to Alzheimer’s, even in Washington, she says, “one roadblock Congress fortunately doesn’t have to worry about is partisanship.” Other roadblocks—budgets, competing priorities—“are harder, but by no means impossible for someone who has personally seen the devastating toll this disease can take.”

Capito has spoken publicly about her parents’ experience with Alzheimer’s. So far in 2019, she participated in the introduction of the Younger-Onset Alzheimer’s Disease Act, the reintroduction of the CHANGE Act, and the announcement of a half-million dollar grant for WVU’s Alzheimer’s research.

Capito expects the RNI’s work to benefit West Virginians directly, and Mark Polak one-ups her optimism. “The first person who’ll be cured is alive today,” he avows. Then he goes further: “So it might as well be Judi, right?”

Years of research lie ahead. Additional trials will take place at Cornell University and elsewhere. If WVU’s results show promise, follow-up trials might target other parts of the brain or deliver immunotherapy or medications through the blood-brain barrier. Not only Alzheimer’s specialists, but physicians and patients fighting other incurable brain diseases, such as Parkinson’s and glioblastoma, are awaiting WVU’s results, all over the globe.

But, Rezai acknowledges, “while we work very hard to find cures or treatments, it’s important that we don’t lose sight of people like Judi and their families, who are living with Alzheimer’s every day.” He’s impressed by West Virginia CARES, for Coordinated Action, Response, Education, and Support, a program that trains professionals across different sectors, such as the faith or banking communities, to recognize and respond to dementia. With Marshall Health at Marshall University, which has its own multi-pronged Alzheimer’s response, WV CARES also trains health care professionals and first responders. In April, it certified the Boone County Sheriff’s Department as the state’s first 100 percent–certified dementia-friendly department.

The first sets of data from PET scans and the memory and cognition testing aspects of the trial will be ready in the fall of 2019, and monitoring will continue for up to five years. Mark, Judi, and others believe they can see a change, a sparkle in Judi’s eyes since the procedures. Still, the trial has brought challenges. They think Judi may be more frustrated than before the procedures, because the improvements they feel she has made enhance her awareness of her own slippages and missed connections.

Judi more readily admits dejection, while Mark rallies a fierce optimism. He celebrates their coping tools: a calendar, a system for medications, written directions for the new washing machine, home cameras, an app for tracking Judi when she drives. He notes “little moves forward and an occasional step backward.”

“Right,” says Judi neutrally.

“She sees the step backward,” says Mark.

“I do,” she says.

They are equally committed, though, to the WVU trial.

“Even if it didn’t do anything—” Mark begins.

“It means something,” says Judi.

“It means something,” Mark agrees.

One aspect of the trial monitoring does shake Mark’s tireless positivity: the interviews during which he reports on Judi’s condition. He describes those as “very negative” and “really focused on what’s bad. It’s like, ‘Why don’t you ask me what’s good?’” The questions Mark wants to answer, he says, are: “Tell me one good thing that has happened this week,” and, “What have you done to fight this disease?”

Judi misses her work, the camaraderie of her team at the HSC, “terribly.” But she continues to heal others. She volunteers to cuddle babies in the neonatal intensive care unit. Meanwhile, Judi maintains, the most important thing she or any patient can do is “not quit.”

Mark agrees. “You have to be involved. You have to fight things. It’s always people ‘suffering’ from Alzheimer’s. They no longer ‘suffer’ from cancer, now they ‘fight’ cancer, they ‘fight’ ALS, they ‘fight’ MS. But you suffer from Alzheimer’s, you die from Alzheimer’s. We wanted to change that scenario. We wanted to be part of the cure in any way we could.”

Resources for Alzheimer’s


WV CARES is a one-stop shop connecting dementia-affected individuals and families to resources including the Bureau of Senior Services, AARP, the Alzheimer’s Association, and other local support systems. wvcares.org

The Alzheimer’s Association provides free support to anyone affected by any form of dementia. Staff help individuals navigate the local resource landscape, coordinate conference calls between family members, and help match patients and families with volunteer educators or clinical trials. alz.org, 1.800.272.3900

by Micaela Morrissette

photos courtesy of WVU Medicine

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