New Parkinson’s treatment developed at Stanford could help millions

After a twitching pinky finger led to a diagnosis of young-onset Parkinson’s disease, Keith Krehbiel, then 42, stopped at a bookstore on the way home to learn more about the progressive neurological disorder before telling his wife Amy the shocking news.

“I remember sitting in a parking lot and hearing this sad piece by Miles Davis,” he said. “I haven’t been able to listen to it since without feeling what I felt then.”

Twenty-eight years later, as a political science professor emeritus at Stanford, Krehbiel just became the first person in the U.S. to receive adaptive Deep Brain Stimulation (aDBS) therapy as a part of regular care. It had previously been available only on an experimental basis.

The therapy is akin to a pacemaker for the brain, counteracting beta waves and other arrhythmias relating to the immobility, stiffness and trembling associated with Parkinson’s. The device functions in a closed loop within the body, responding in real-time to feedback from the brain while documenting these interactions.

None of this was possible until Stanford researchers developed it in 2015 by implanting the first-generation sensing neurostimulators. Now, the personalized treatment is poised to touch millions of lives.

Parkinson’s disease diagnoses have doubled since the 1990s, affecting 10 million people around the world, including “Back to the Future” icon Michael J. Fox and science communication advocate Alan Alda of M*A*S*H fame.

A study published this month predicts that 25 million people worldwide will be living with the disease by 2050. The U.S., where a million people have the disease, reports 90,000 new diagnoses each year.

The emerging aDBS therapy is a quantum leap from earlier treatments, approved by the FDA in 1997, the same year Krehbiel was diagnosed. In both, currents from a battery-powered neurostimulator in the chest are sent to two electrodes in the brain via wires extending up the neck, behind the ear, and into the head.

Dr. Helen Bronte-Stewart, the Stanford neurologist whose research contributed to the development of the new therapy said older versions were “basically blind and deaf to the brain’s own rhythms.”

The over quarter-century-long road to aDBS began when Bronte-Stewart was growing up in the U.K., training to be a ballerina. When she chose science, her fascination with movement brought her to lead Stanford’s movement disorders center in 1999.

Her work gravitated toward Parkinson’s because of how kinetically complex and common the disease is — second only to Alzheimer’s in prevalence among degenerative neurological conditions and fastest-growing globally.

In 2011, Medtronic, a medical device company headquartered in Dublin, Ireland, sought programming for their new sensing neurostimulator. They had the platform, Stanford had the technology and Bronte-Stewart had the science.

By 2018, projects across the U.S., Canada and Europe catalyzed an international multi-center pivotal trial for market approval of aDBS.

“This was fairly radical,” said Bronte-Stewart, whose team went from applying aDBS for 20 minutes at a time in the lab to sending subjects home with it.

In 2020, Krehbiel was originally scheduled for the earlier treatment, cDBS but qualified for experimental aDBS after the COVID-19 pandemic delayed his implantation.

Neurosurgeons drilled two holes into his skull while Krehbiel was fully conscious — a “creepy” experience despite the absence of pain. After a night at home with bandages securing the “manhole covers” in his head, he returned to the hospital, went under general anesthesia, woke up while doctors fit electrodes into his brain, and slept again.

Minus a slight headache when he awoke, Krehbiel felt better even before the system was on.

“My tongue felt like it had helium in it — it levitated to the top of my mouth,” he said, of the “tweaking” process that acquainted aDBS to his unique biology.

Krehbiel gradually went from six or seven pills of dopamine agonists a day to one, freed from the “awful” side effects of the drugs commonly prescribed for Parkinson’s.

Krehbiel’s disease continues to progress, in the forms of vocal deterioration, fainting spells and falls, but life is better, he said.

“It’s definitely a game changer but it’s not a cure,” he said.

Across the Bay, on Alameda island on a recent Friday afternoon, John Lipp, another Stanford research subject, unbuttoned the pink sateen shirt under his blue blazer. Standing in the open doorway to the dog kennels of Friends of the Alameda Animal Shelter where he is the CEO, he asked his colleague to cue up a “stripper song” — “You Gotta Have A Gimmick” from the musical “Gypsy.”

He flashed a red line on his chest, where surgeons slid a fresh neurostimulator under his skin in an outpatient procedure in December. Soon, he won’t have to go under the knife to recharge the device.

Lipp learned he had Parkinson’s in 2015. He was 49. A harbinger had been when he was on his way to meet friends and his hand clenched into a fist. “I literally stopped in the middle of the street and talked to myself: ‘Hey, relax.’”

After diagnosis, Lipp ran his first marathon at Disneyland in 2016 but soon had to stop running because of severe muscle cramping.

In 2019, his care team told him about a study in which he could receive cutting-edge treatment while advancing medicine.

He went into surgery ready, panicking only when he realized his head was locked to the operating table. Establishing care afterward was rocky. When he worried about travel plans with his husband, researchers told him he could quit the trial. But, he thought, I’ve come this far.

The aDBS treatment banished Lipp’s cramping and helped him shed most medications. Last November, he completed the 2024 New York City Marathon.

“Even if the DBS is working, the Parkinson’s is progressing, even hour by hour,” Lipp said. Anxiety, insomnia, stress and a gait that’s slightly off remain part of his reality. He can no longer open his eyes in the morning without prying them open manually.

Lipp is retiring this June, in part, to focus on his health and advocate for the Parkinson’s community.

“One thing I’ve learned about this disease – any disease – is that it doesn’t change your nature. If you’re an optimistic person before your diagnosis, you’re going to be after it,” he said.

Brian Fiske, chief scientist at The Michael J. Fox Foundation for Parkinson’s Research, which funded some of Bronte-Stewart’s early aDBS research, said no approved treatment exists to slow Parkinson’s. “But we see these advances in symptom management to be just as critical,” he added.

An international registry will follow participating aDBS patients to inform further advancements. The pre-existing treatment is still in use in some patients — its steady signal is still optimal for some, especially if their neural signals are too weak for aDBS responses.

Bronte-Stewart expressed gratitude for supporters of research, and human subjects who spend years in trials with no guarantee of benefit. She wants the new treatment to reach everyone who needs it.

“Only 2% of doctors become neurologists, and yet, neurological diseases are increasing exponentially. So you can immediately see there’s a supply and demand problem,” she said.

If Bronte-Stewart ever finds free time, she dances — keeps it moving.

“This is just the beginning,” she said.