Altering the course of Parkinson's Disease

With the support of the National Institutes of Health, a groundbreaking new study led by Dr. Craig van Horne aims to not only halt Parkinson’s disease in its tracks but also reverse its effects.

This Kentuckian’s experience with an innovative clinical trial is a beacon of hope for many battling Parkinson’s disease.

It all began when Hoyt “Corky” Ball’s right hand began to tremble uncontrollably. The 69-year-old knew something was wrong. The tremors impacted his work in construction and as a school bus driver.

His primary care doctor initially ruled out Parkinson’s, but the prescribed medication failed to alleviate his symptoms. That’s when his sister urged him to see Zain Guduru, MD, a neurologist with the UK Kentucky Neuroscience Institute and associate professor in the University of Kentucky College of Medicine. Within 10 minutes of meeting Dr. Guduru, Ball received a definitive diagnosis: It was, in fact, Parkinson’s. Ball didn’t know much about the movement disorder at first.

“My first question was: How long do I have?”

Guduru reassured him that Parkinson’s is treatable and suggested a method called deep brain stimulation (DBS). DBS is described as a “pacemaker for the brain.”

By placing electrodes within malfunctioning brain pathways, DBS disrupts abnormal signals that cause tremors and other symptoms.

A revolutionary clinical study

As Ball began researching his diagnosis and treatment options, he came across UK HealthCare neurosurgeon Craig van Horne, MD, PhD, and his work on a procedure known as DBS-Plus. Van Horne is co-director of the UK HealthCare Neurorestoration Center (NRC) and a team of physician-scientists and researchers leading a first-of-its-kind clinical study aimed at stopping or reversing the degenerative effects of Parkinson’s disease.

The study combines DBS with an experimental nerve-grafting procedure. The nerve cells are transplanted during DBS surgery, meaning patients do not have to undergo additional procedures.

In this combined approach, known as DBS-Plus, the surgeon transplants peripheral nerve tissue into an area of the brain where neurons are dying. The grafted cells are being tested for their ability to release chemicals believed to rejuvenate the brain’s weary dopamine-producing neurons. Van Horne and his team take a small piece of nerve tissue from the patient’s ankle and implant it in their brain.

Because the tissue is from the patient’s own body, there are no concerns about rejection.

The grafting procedure has been proven relatively safe with only minimal additional risk through the work that van Horne and team have conducted.

Focusing on disease progression

Scientists have long known that peripheral nerves, which exist outside the brain and spinal cord, possess regenerative qualities that central nervous system nerves do not. The UK team hopes to leverage those regenerative effects within the brain, potentially halting or reversing nerve damage caused by Parkinson’s.

“While the peripheral nervous system can repair itself, the central nervous system does not do a very good job of it,” said van Horne, the study’s principal investigator. “The question is: Can we tap into the ability of the peripheral nervous system’s response for repair? Can we bring this biologic intelligence to the central nervous system?”

To test the effect of the graft, researchers can turn off the DBS pulse generator and evaluate patient’s symptoms at a baseline level.

The team’s vision is to alter the course of Parkinson’s.

“Our concept for DBS-Plus, the ‘plus’ part being the nerve grafting, is disease modification,” van Horne said. “Previously, all of the other transplant models were looking at symptoms and not disease progression. From that standpoint, that’s where we can say the DBS-Plus has its big advantage.”

Parkinson’s disease is a progressive disease. Once it starts, there are currently no treatments that will prevent it from worsening.

“You can give medications, you can even do deep brain stimulation, and you can treat some of the symptoms, but you don’t stop the progression. That’s what we are trying to fix,” van Horne said. “What we really want to determine is this: What is it going to take to get patients to a better place? It is not going to be one-size-fits-all.”

The incredible impact of DBS-Plus

Intrigued by the potential of DBS-Plus to not only help him but also advance medical understanding, Ball decided to participate in the clinical trial.

“I really didn’t want to have DBS without doing DBS-Plus. It might not help me, but it may help somebody later,” he said.

Ball’s journey with DBS-Plus began in February 2023, and he has since experienced remarkable improvements. Before DBS-Plus, his tremor made daily tasks nearly impossible.

“Talking to somebody, my hand just went crazy. I couldn’t do anything with my right hand,” he said.

It was a tough reality for someone who was often on ladders and rooftops working in construction. But today, Ball reports being 90% better. He goes in for appointments every two to three months to see if any adjustments need to be made.

“I don’t think I will ever be 100%, but my life has improved greatly. My overall health is better. You can’t tell I ever had Parkinson’s,” he said with a smile.

Ball said his medication has reduced from 12 pills a day to just three. He’s able to continue his work as a school bus driver in Nelson County, which he has done for eight years. Plus, he can play guitar again, one of his favorite hobbies.

“It’s been a life-changer for me.”

Momentous support from NIH

Van Horne hopes the nerve-graft will eventually become the new “standard of care” for advanced Parkinson’s. The study is one step closer to that goal after receiving financial support from the National Institutes of Health (NIH) in the summer of 2024.

“This has really legitimized to some degree what we have been working to do,” van Horne said. “To get NIH funding, it has to go through many committees of researchers and clinicians who review the work, they compare it to other people’s work and if you’re successful and they think it’s worthwhile, then they’ll say that it’s worth funding.”

The study is known as the STAR trial. Greg Gerhardt, PhD, John Slevin, MD, and George Quintero, PhD, are leading the work along with van Horne. It spans the departments of neurosurgery, neuroscience and neurology within the UK College of Medicine.

This NIH grant will provide the opportunity to carry out the first double-blinded study of this approach, which is especially important in developing a possible future efficacy trial to fully assess the use of peripheral nerve repair cells.

Until now, researchers have primarily focused on altering the progression of the motor symptoms of Parkinson’s disease. With this grant, they can now begin to evaluate a strategy to alter the progression of nonmotor symptoms of Parkinson’s, in particular cognitive disorders that may overlap with neurodegenerative diseases.

Up until this point, the work has been sustained by philanthropy and community support, which van Horne and the rest of the team are immensely grateful for. It’s an approach that doesn’t generate money, since doctors are using the patient’s own nerve cells.

“For us to get something like this is remarkable,” van Horne said. “We don’t have corporate support. We don’t have company support. We don’t have a good business model. We just want to be able to translate this into better outcomes for patients.”

Ball’s journey underscores the importance of innovative treatments like DBS-Plus.

“My quality of life is better than I could have ever hoped,” Ball said. “I’m doing things I love and celebrating the big milestone of my 50th wedding anniversary this year.”

Now as van Horne and the rest of the team continue their groundbreaking work with the support from NIH, stories like Ball’s emphasize the immense potential to change lives.

“There’s a lot of hope, and now is the chance for us to be able to prove that,” van Horne said.