Historic breakthrough: WVU Rockefeller Neuroscience team first to use ultrasound to treat Alzheimer's

MORGANTOWN — World-leading brain experts at West Virginia University’s Rockefeller Neuroscience Institute are celebrating the historic breakthrough Alzheimer patients around the global have been waiting for.

“For Alzheimer’s there’s not that many treatments available, despite hundreds of clinical trials over the past two decades, and billions of dollars spent,” said Dr. Ali R. Rezai, a neurosurgeon at WVU who led the team of investigators that successfully performed a phase II trial using focused ultrasound to treat a patient with early stage Alzheimer’s.

The WVU team tested the innovative treatment in collaboration with INSIGHTEC, an Israeli medical technology company. Earlier this year, INSIGHTEC was approved by the U.S. Food and Drug Administration to begin a phase II clinical trial of the procedure, and selected the WVU Rockefeller Neuroscience Institute as the first site in the United States for the trial.

Last summer, researchers at Sunnybrook Health Sciences Centre in Toronto reported the results of a phase I safety trial showing that they could reversibly open the blood-brain barrier in Alzheimer’s patients.

The procedure in West Virginia involved the use of ultrasound waves focused through a specialized helmet with more than 1,000 probes targeting a precise spot in the brain, Rezai explained, coupled with microscopic bubbles.

“And when we put a different frequency of ultrasound on the bubbles they start osculating,” he said.

The reaction opens up the brain-blood barrier — a nearly impenetrable shield between the brain’s blood vessels and cells that make up brain tissue.

“It’s protected on one end for us to function but also prevents larger molecules or chemotherapy or medications or anti-bodies or immune system cells or amino therapy or stem cells to get in,” he said.

In this case, the West Virginia team targeted the hippocampus and the memory and cognitive centers of the brain which are impacted by plaques found in patients with Alzheimer’s.

“Plaques are these clusters of proteins that accumulate and they block-up the brains connectivity,” he said. “In animal studies it showed that these plaques are cleared with ultrasound technology.

The first patient, a person Rezai called a pioneer and hero is West Virginia health care worker and former WVU Children’s Hospital Neonatal Intensive Care Unit nurse Judi Polak.

“I think that with Alzheimer’s there’s so much in the unknown and I’ve been with Health Science for a long time and I understand that we need to be able to step forward and look into the future,” Polak said.

But getting to this point was a long journey beginning five years ago when she was first diagnosed with early-onset Alzheimer’s.

“That took me a while to deal with,” Polak admitted while sitting with her husband of 36 years, Mark Polak. “It was hard to say that I have Alzheimer’s. I didn’t want to be the person who felt sorry for myself and so we looked at clinical trials as a way to help not only me but other people too.”

Early-onset Alzheimer’s is an uncommon form of dementia that strikes people younger than age 65. Of all the people who have Alzheimer’s disease, according to research conducted by the Mayo Clinic, about 5 percent develop symptoms before age 65.

Judi Polak’s willingness to be the center of a study or research experiment in hopes of finding a cure for Alzheimer’s took an emotional toll, Mark Polak said, referring to a controlled drug-placebo trial at the University of Pittsburgh several years ago.

“Guess what, the drug didn’t work,” he said with contempt. “Just like every drug that has been tried doesn’t work.”

However, Judi Polak’s patience and persistence appears to have paid off. The procedure, which lasted three hours, safely and successfully opened her blood-brain barrier for a record 36 hours.

“It was opened longer than they expected,” Mark Polak said. “They were actually, I think both excited and scared. The team was ecstatic.”

One member of the team Mark Polak mentioned is Dr. Jeff Carpenter, a professor of neurology, neurosurgery and an interventional neuroradiologist at WVU.

“This is really step one,” Carpenter said of the successful trial. “This is to make sure it’s safe and hopefully we can decrease some of the big plaques in that part of the brain.”

Carpenter is what he jokingly called the “technical guy” on Rezai’s team with 18 years of experience working MRI technology and interventional radiology.

“It’s a combination of knowing MRI very well and also being used to actually treating patients,” Carpenter said. “This treatment marries MRI guidance with ultrasound targeting. “It really uses all the things I’ve been working with.”

Carpenter, a native of Fairmont, credited Rezai’s work and ultimately the leadership at WVU Medicine for supporting the research needed.

“It is really nice to be able to do this level of work this close to home,” he added.

The potential benefits of the first and subsequent treatments will take several years to fully evaluate, Rezai said. Two more similar procedures are scheduled for Judi Polak; one on Tuesday and a final test in November.

“I am hopeful that focused ultrasound opening of the blood-brain barrier will prove to be a valuable treatment option for Judi Polak and other patients with early Alzheimer’s who are confronting the enormous challenges associated with the disease on a daily basis,” Rezai said.

Although Rezai stopped short of giving any immediate results from the first treatment, Polak said she noticed a change the next day.

“I think I could speak clearer and did not wait as long in answering questions,” she said. “Sometimes in the past things would leave my mind and I couldn’t remember things.”

“This is man on the moon stuff,” Mark Polak said of his wife’s success in the first trial. “Maybe we’re on to something.”

Could some ADHD be a type of sleep disorder? That would fundamentally change how we treat it.

ver the past two decades, U.S. parents and teachers have reported epidemic levels of children with trouble focusing, impulsive behavior and so much energy that they are bouncing off walls. Educators, policymakers and scientists have referred to attention-deficit/hyperactivity disorder, or ADHD, as a national crisis and have spent billions of dollars looking into its cause.

They've looked at geneticsbrain developmentexposure to leadthe push for early academics, and many other factors. But what if the answer to at least some cases of ADHD is more obvious?

What if, as a growing number of researchers are proposing, many kids today simply aren't getting the sleep they need, leading to challenging behaviors that mimic ADHD?

That provocative and controversial theory has been gaining momentum in recent years, with several studies suggesting strong links between ADHD and the length, timing and quality of sleep. In an era in which even toddlers know the words Netflix and Hulu, when demands for perfectionism extend to squirmy preschoolers and many elementary-age students juggle multiple extracurricular activities each day, one question is whether some kids are so stimulated or stressed that they are unable to sleep as much or as well as they should.

Growing evidence suggests that a segment of children with ADHD are misdiagnosed and actually suffer from insufficient sleep, insomnia, obstructed breathing or another known sleep disorder. But the most paradigm-challenging idea may be that ADHD may itself be a sleep disorder. If correct, this idea could fundamentally change the way ADHD is studied and treated.

The latest data on this topic, presented this month at the European College of Neuropsychopharmacology Conference in Paris, looked at people's circadian rhythms — the natural cycle of how they sleep and wake. It showed that study subjects with ADHD had levels of the hormone melatonin that rose 1.5 hours later in the night than those without ADHD. As a result, they fell asleep later and got less sleep overall, with consequences for other body processes.

When the day and night rhythm is disturbed, explained researcher Sandra Kooij of the Vrije Universiteit Medical Centre in Amsterdam, so are temperature, movement and the timing of meals. Each change can lead to inattentiveness and challenging behavior.

"[I]t looks more and more like ADHD and sleeplessness are two sides of the same physiological and mental coin,” Kooij said in her presentation.

Sleep problems fall into three categories: insufficient sleep, insomnia and disordered breathing. All are common among young children. Some studies estimate that their prevalence might be as high as 20 to 40 percent in young children.

Karen Bonuck, a professor of family and social medicine at Albert Einstein College of Medicine in New York, is known for her work on a 2012 study of 11,000 children published in the journal Pediatrics. It found that those with snoring, mouth breathing or apnea (in which a person's breathing is interrupted during sleep) were 40 percent to 100 percent more likely than those without the sleep issues to have behaviors resembling ADHD by age 7.

There's a lot of evidence that sleep is a big factor in behavior in children,” Bonuck said in a recent interview.

Previous studies have shown that about 75 percent of people with ADHD have sleep disturbances and that the less sleep they get the more severe the symptoms. In one paper, scientists showed that a group of children with nighttime breathing issues who were diagnosed with ADHD no longer met the diagnostic criteria for the disorder after they had their adenoids or tonsils removed to treat the sleep problem.

Bonuck's recent work, funded by the National Institutes of Health, involved an education campaign targeted at teachers, parents and children that used teddy bears and the classic book “Good Night, Moon” to encourage more sleep. When researchers were collecting baseline data before any interventions, she said, she was shocked to find that a number of preschool children were going to sleep at 11 p.m. or later but had to be up before 8 a.m. to go to school. They were getting less than nine hours of sleep, markedly less than the 10 to 13 hours the American Academy of Pediatrics recommends for children ages 3 to 5.

“I thought there was an error,” Bonuck recalled. “Challenging behavior is a huge problem in the classrooms on a national level, and the symptoms of lack of sleep can look a lot like the symptoms of ADHD.”

William E. Pelham, a longtime ADHD specialist who directs the Center for Children and Families at Florida International University, agrees that some children are misdiagnosed as having ADHD when they actually have a sleep problem. Yet he said he has seen this only in a “handful” of cases out of thousands.

The link, he contends, is overstated and ADHD is a very real and potentially very serious diagnosis. According to the most recent survey by the Centers for Disease Control and Prevention, about 6.4 million children, or one out of every 10 children ages 4 to 17 in the country, have been diagnosed with ADHD, and he believes that the diagnosis is correct in most cases.

“Sleep is an issue for anything where you are trying to measure attention. But I don't believe [it] … accounts for the vast majority of ADHD in the United States,” he said. 

Still, Pelham has noticed an increasing number of children with ADHD and sleep issues in recent years. That has less to do with the nature of ADHD than with changes driven by the pharmaceutical industry, he said.

In the 1980s and 1990s, the most popular treatments were stimulants that acted only for four to six hours. Most kids now are taking ones that last 12 hours, he said.

“If you have kids who are sensitive to the medications. they might not be tired until midnight. So you have an increase in kids staying up later as a result of a societal shift of using the longest-acting medication,” he explained. Then, to counteract that in the evening, more children are taking yet another drug — “an antidepressant, melatonin or, God forbid, an antipsychotic,” he said.