Clinical trial offers hope to those with Parkinson's

 

Grady Harris, 67, participated in a clinical trial in which focused ultrasound was used to stop his tremors from Parkinson's disease. He was photographed Thursday, March 12, 2015.  (Bill Tiernan | The Virginian-Pilot)

 

Ann Perkins, who was diagnosed with Parkinson's disease in 2000, works out at the Great Neck Recreation Center in Virginia Beach on Thursday, March 19,2015. (Bill Tiernan | The Virginian-Pilot)

By Elizabeth Simpson

The Virginian-Pilot

© April 1, 2015

The first symptom, a shaky hand, surfaced a decade ago when Grady Harris was sanding his boat.

Harris, who was 57 at the time, thought it was the strain of the sanding, but his brother noticed the tremors, too.

It turned out to be the beginnings of Parkinson's disease, a progressive nerve disorder that affects a million Americans.

Hundreds of symptoms have been chronicled over the years, including a vanishing sense of smell and severe muscle loss.

A signature indicator is tremors - involuntary, rhythmic movement of a hand, arm, leg or other body part.

Medications kept those at bay for Harris, a Virginia Beach resident, for many years, but as the disease progressed, the shaking in his right hand picked up.

Some treatments for Parkinson's struck Harris as too invasive, such as deep brain stimulation, in which wires implanted in the brain send electrical impulses to stem the tremors.

But several years ago, a University of Virginia doctor who was treating Harris said he'd be a good candidate for something new that would not involve scalpels or opening his skull: focused ultrasound.

The idea is to zap tremor-causing nerve cells in the brain by focusing intersecting sound waves on them without damaging surrounding tissue - sort of like holding a magnifying glass above a leaf so that intensified light can burn a tiny spot.

Harris said yes to a clinical trial that would be conducted by doctors at two U.S. hospitals, the University of Virginia Health System in Charlottesville and Swedish Medical Center in Seattle.

His experience offers a window into the world of Parkinson's disease and scientific efforts to find new hope for patients.

Ultrasound mainly has been used for diagnostic purposes, such as capturing images of a fetus during pregnancy.

These days, the technology is used routinely to check for internal conditions such as kidney stones, heart defects or dangerous fluids.

Focused ultrasound, however, goes beyond diagnosis to treatment. An MRI guides highly focused, intersecting ultrasound beams to zap cells deep within the body. While this use is still mostly under clinical study, it has the advantage of being noninvasive, so recovery is quicker, and the process is less expensive.

The U.S. Food and Drug Administration has approved focused ultrasound to treat uterine fibroids and pain from bone cancer.

Clinical trials are under way at U.Va., exploring the approach for people with Parkinson's and a neurologic disorder called essential tremors that causes involuntary, rhythmic shaking.

In a pilot study in 2011, 15 essential-tremors patients who received focused ultrasound treatments saw improvement, and the results were published in the New England Journal of Medicine. Lead researcher Dr. Jeff Elias said in a recent phone interview that two of the subjects have since had some recurrence of the tremors, but most haven't.

Results from a second, larger study at eight research centers are looking positive, according to Elias, but full findings won't be available until later this year.

Two other clinical trials have been launched to treat symptoms of Parkinson's disease. One group includes people with dyskinesia, which is slow, uncoordinated, abnormal movements. The other focuses on Parkinson's patients whose main symptom is tremors that are resistant to treatment.

That study is the one that Harris, who is now 67, enrolled in as a subject.

Going into the study, Harris was told he'd receive either the treatment or a sham, in which he'd go through the MRI machine and all the steps of the treatment, except with no ultrasound beams.

He hoped he'd get the real thing, but he was committed to doing whatever he could to further research into his condition. Also, those who received the sham treatment would eventually be offered the real one.

In addition to worsening tremors, he was experiencing stiffness, imbalance, fatigue and muscle soreness.

Before the procedure, he had an all-day assessment of his cognitive abilities, balance and agility, along with blood and psychological evaluations.

In December 2012, he went to a focused ultrasound clinic at U.Va. They shaved his head, then placed it in a halo-like device with four prongs to hold it perfectly still. He lay motionless in the MRI machine as his brain was scanned, and ultrasound rays beamed into a middle region of the brain called the thalamus, where faulty circuitry causes tremors.

Harris remained conscious and able to answer questions throughout the 4-1/2- hour process.

At first, he didn't feel anything when told the first of a series of procedures was beginning. As they continued, though, he felt a little dizzy. Then, very dizzy. Finally, he felt a wave of head pain come over him, and a sense of pressure.

There was a button he could press if he wanted to stop, but he endured.

The sensations, though intense, also gratified him because they led him to believe he was indeed getting the real treatment.

He was growing tired when Elias asked whether he could do one last procedure.

Harris said yes. "I was relieved to know there was only one more."

After that, he was taken to a hospital room where his wife awaited him.

He was so tired, he didn't notice the one thing that had brought him there in the first place.

His wife pointed it out:

His hand had stopped shaking.

"My hand was as steady as this table," he said. "That's when I realized, 'Hey, this is cool. This is good.' "

The next day, he drove home to Virginia Beach.

Harris' experience is the kind that grabs the attention of people like Ann Perkins.

A 64-year-old who lives in Virginia Beach, Perkins was diagnosed with Parkinson's when she was 48.

She worked as a pharmaceutical representative at the time and happened across a pamphlet in a doctor's office that said, "Has your handwriting become smaller?"

Hers had, so she read on and found out it was a symptom of Parkinson's disease. She had another symptom on the list, too: losing her sense of smell.

Diagnosed soon after that, she kept her job for 10 years but quit after she fell down at work. She's now an advocate for Parkinson's education and services, and she runs a local support group through the American Parkinson Disease Association.

Medication helps her symptoms, but they have gradually worsened. "I am feeling fine now, but it takes a lot of work. From the time I wake up till the time I go to bed, I'm thinking about what I can do to manage my symptoms." She does drills to keep her voice strong, stretches to keep muscles from tightening, exercises to keep limber.

She doesn't like the idea of having holes bored into her head to insert electrodes for deep brain stimulation, nor of having to replace their batteries periodically.

Not long ago, she saw a news show about focused ultrasound for Parkinson's patients in Israel and Switzerland. It mentioned work being done at U.Va. She called and had her name put on the list. "Grady Harris beat me to it," she said with a laugh.

She said the studies give the Parkinson's community hope.

That's something Dr. Neal Kassell hears from people with various diseases he says could be helped by focused ultrasound. He was co-chairman of the Department of Neurology at U.Va. and is founder and chairman of the Focused Ultrasound Foundation in Charlottesville.

Kassell said research is under way across the globe in areas of epilepsy, brain tumors, prostate cancer, Alzheimer's disease and many other illnesses.

"The level of interest is exploding," he said.

Harris eventually learned he did get the real treatment.

Deep in his heart, he knew it. For weeks, he showed friends how his hand had stopped shaking and described the clinical trial.

"People said, 'You let them to do that?' There's a lot of people who wouldn't do it. I'm glad I was considered for it."

He was examined the next day, and again at one week, one month, three months, six months and a year.

Two months after the procedure, Harris' tremors began coming back.

He said Elias told him he could try again once the study is finished, if the FDA approves focused ultrasound for use.

Elias can't talk about the complete results of studies that are ongoing.

Harris continues his work at a Charles Barker auto dealership in Virginia Beach, where he oversees used-car acquisition. He still plays golf, "but not very good," he says.

The losses of Parkinson's continue apace. "My memory is nowhere near what it was. You lose your train of thought."

He's starting to have tremors in his right leg and the right side of his face, as well.

Still, he appreciated being able to participate in the study.

"To have the opportunity to improve my quality of life in any way, to not take advantage of that would be a waste. I think if I hadn't had it done, the progression would be worse."

He wants to wait and see the final results of the study - expected later this year - before deciding whether to try it again.

Elizabeth Simpson, 757-222-5003, elizabeth.simpson@pilotonline.com

http://hamptonroads.com/2015/03/clinical-trial-offers-hope-those-parkinsons