UK Parkinson's research offers hope, promise

LEXINGTON, Ky. – Standing at the pulpit, leading a congregation in song, Bill Crawford felt a familiar, foreboding numbness in his toes.

Within seconds, those toes curled down in his shoes like a bird clamping onto a wire. Pain spread through his feet and up his legs, twisting them to one side. He knew what came next: Uncontrollable muscles cramping and twisting his body and neck.

Trying to stop this “full-body charley horse,” Crawford laid down near the piano as the congregation kept singing.

Such episodes were an all-too-common part of Crawford’s life with Parkinson’s disease until last year, when an experimental procedure at the University of Kentucky gave him back control of his body. The technique, part of a first-ever clinical trial, involves implanting pieces of a nerve from near a patient’s ankle into the brain during a neurosurgical procedure known as deep brain stimulation. It's showing promise against the devastating movement disorder that proved the toughest foe for the late boxing legend and Louisville native Muhammad Ali - and millions of others. 

“God works through doctors and surgeons and gives them wisdom and knowledge in order to help folks,” said Crawford, 56 ( 57 Dec. 29), worship leader of singing at Porter Memorial Baptist Church. “I forget how blessed I am to be able to do the things I’m still doing.”

Since Crawford’s August 2015 surgery, he's never had another “charley horse” episode and moves far more smoothly and easily than before. Most other study subjects whose progress has been tracked so far have also seen important gains.

Dr. Craig van Horne, who is leading the research, said the nerve pieces help rejuvenate dying neurons in a part of the brain that helps control movement. “You’re stimulating the dying neurons to not die,” he said. “You’re basically providing fertilizer.”

Van Horne said he and his colleagues are excited by the possibilities for treating Parkinson's, a chronic, incurable disease that afflicts 10 million people worldwide, including more than a million Americans.

“We need to do what we can to stop it,” said researcher Dr. Greg Gerhardt. “The disease marches on relentlessly.”

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Decline, desperation

Crawford never expected Parkinson’s to strike him when he was only 42.

It began with vague symptoms - weak knees and occasional overall weakness. Then his right hand began trembling. His face got droopy. About a year and a half after the first sign of a problem, doctors gave him the official diagnosis and started him on medications.

They didn’t help much. The charley horse episodes began, getting worse and more frequent over time. When they hit in church, he would try to make it off the stage so as not to distract the service – but sometimes couldn’t get that far. While he worried about making a spectacle, he said he felt an outpouring of love, acceptance, and support from the congregation.

At their worst, the episodes struck three and four times a day. Once, Crawford’s wife Lisa had to pull their car over when an attack began in the passenger seat.

“Before I had the surgery, my life was unpredictable,” said Crawford, who with Lisa had four children, one of whom died of a brain tumor two years ago. “Parkinson’s is so different for everybody. You don’t know what it will affect.”

Eventually, walking became a challenge. A video taken by the research team shortly before Crawford’s surgery shows him shuffling with his feet turned in, taking tiny steps. His body leans slightly sideways. His head is turned to the side. When he stops, his right arm and hand shake.

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Out in public, “people sometimes thought he was drunk,” Lisa said. Security workers would follow him around during shopping trips to Wal-Mart.

Doctors talked to Crawford about Deep Brain Stimulation, or DBS, which is for patients whose symptoms aren’t well-controlled with medicine alone. It involves implanting a battery-powered neurostimulator to deliver electrical stimulation to targeted areas of the brain. Crawford learned about the clinical trial and figured it might offer even more benefits.

Brain surgery was a scary prospect, Crawford said, “but at that point, I was kind of desperate.”

The procedure took place in two stages a few days apart, with the DBS and nerve implantation surgery lasting about seven hours. Doctors harvested a nerve from just above Crawford’s ankle, cut it into pieces, and grafted it into his brain while also implanting the DBS electrodes and neurostimulator.

“I went into it trusting God was in control,” Crawford said. “I felt like I was in good hands.”

Future hopes

Van Horne said the research harnesses the regenerative power of peripheral nerves, those outside of the brain and spinal cord with cells that can transform into repair cells after injury. The nerve pieces go into a part of the brain where the chemical dopamine, which is gradually lost in Parkinson’s, is produced. The goal is to help the brain heal itself.

So far, 34 patients have undergone the procedure. Of the 17 who had surgery at least a year ago, 11 showed “clinically important improvement” in motor performance when taken off their medicine briefly for testing. Three of four at the 6-month mark saw similar improvement from where they were before the surgery. Without treatment, van Horne pointed out, all would have continued to deteriorate.

Dr. Michael Okun, national medical director of the Parkinson’s Foundation, said van Horne and Gerhardt are pioneers in so-called "DBS-Plus" approaches, and pairing a successful surgery like DBS with nerve growth factors is "highly innovative and interesting."

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"We look forward to learning from the data as it evolves and helps to shape the field," said Okun, who is not involved in the research.

UK’s Institutional Review Board said there have been no adverse events related to grafting the nerve onto the brain, and two such problems related to taking nerve tissue from the ankle, both of which have been resolved. Doctors said a quarter of patients can expect some sort of problem, such as a headache or an issue with the DBS equipment, and all face the normal risks of surgery.

More research is needed, doctors say, including an expanded, multi-center clinical trial. Funding for the current study comes from UK, the National Institutes of Health and private donations. Ann Hanley, who has Parkinson's and is married to WinStar Farm's General Manager David Hanley, has reached out to the thoroughbred horse community to raise money for the research, helping bring in more than $500,000 through the Ann Hanley Parkinson's Research Fund at UK.

"There's no Big Pharma paying for this, and when you don't have Big Pharma behind you, it takes funding," said Hanley, who shadows van Horne as he sees patients. "I'm anxious for a cure and my skin is in the game. I kind of stepped back and asked: 'How can I help these brilliant people achieve their dreams?'"

If the procedure ever becomes widely used, van Horne said it would only add a few thousand dollars to the cost for patients already undergoing DBS – and would likely be covered by insurance, as DBS generally is today.

Crawford said he prays that his experience helps others. Parkinson’s is far less intrusive in his life these days. He still fights a small tremor in his right arm and hand, and his voice has grown quieter, his singing softer. But Lisa said his battle has helped him grow and inspired others.

“Here at church, he worries about being a hindrance to the worship service. But just on a personal, spiritual note, it’s just amazing,” she said. “People look and see you struggling and still praising God. It encourages them to say, ‘If he’s got that issue, then this thing in my life, I can handle.'”

Crawford paused for a moment, looking out at the empty pews in the church where he's worked for more than two decades.

“I still pray for complete healing and restoration,” he said. “God may choose to do that and He may not. But I’m still going to serve Him and praise Him for as long as I can - as long as he gives me breath.”

Reporter Laura Ungar, who also reports for USA TODAY, can be reached at (502)582-7190 or lungar@courier-journal.com.

To donate: Contact Ann Hanley at 859-983-9229 or ann.hanley@uky.edu