At 69, Hoyt "Corky" Ball knew something was wrong when his right hand began to tremble uncontrollably. His primary doctor ruled out Parkinson's, but the prescribed medication failed to alleviate his symptoms. It wasn't until Ball met Zain Guduru, M.D., neurologist with the Kentucky Neuroscience Institute and associate professor in the University of Kentucky College of Medicine, that he received a definitive diagnosis.
"In about 10 minutes, he knew I had Parkinson's," Ball said.
Guduru suggested a treatment 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 causes tremors and other symptoms.
As Ball began researching his diagnosis and suggested treatment, he came across UK HealthCare's Craig van Horne, M.D., Ph.D., and his work on a procedure known as DBS-Plus. Van Horne, who is a neurosurgeon, 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 the 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, now 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. Because the experimental treatment is applied during a procedure that was declared safe and effective by U.S. Food and Drug Administration decades ago, DBS-Plus is considered relatively safe with only minimal additional risk.
Since the 1800s, scientists have 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. "So, the question is can we tap into the ability of the peripheral nervous system's response for repair. Can we bring that to the central nervous system?"
To test the effect of the graft, researchers can simply 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 and 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," said van Horne. "What we really want to determine is, 'What is it going to take to get patients to a better place?' It is not going to be just one thing and one-size-fits-all."
Intrigued by the potential of DBS-Plus to not only help him but also advance medical understanding, Ball decided to participate. "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 remembers. It was a tough reality for someone who was often on ladders and rooftops working in construction.
Today, Ball reports being 90% better.
"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 says his medication has reduced from 12 pills a day to just three. "I've been able to continue my work as a school bus driver in Nelson County, a job I have done and love for eight years now. I also can play the guitar again which is also something I love to do."
Van Horne hopes that DBS-Plus will eventually become the new "standard of care" for advanced Parkinson's. This summer the work took a big step towards that, receiving its first ever support from the National Institutes of Health (NIH). "This has really legitimized to some degree of what we have been working to do," said van Horne.
"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, Ph.D., John Slevin, M.D., and George Quintero, Ph.D., 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. A double-blinded study is a type of clinical trial in which neither the participants nor the researcher knows which treatment or intervention participants are receiving until the trial is over. The approach is keenly 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 which 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.
"The concept of these trials and the work that we've done, have all been generated by us," said van Horne. "This is not part of a company. We're not trying to form a company. We're not trying to develop a product that we're going to take to market and sell. We are really trying to just solve this problem. The NIH is really good about funding the basic science, but when it comes to translating and furthering the work to show it is really effective…who is going to help pay for that research? That usually falls on the shoulders of drug or device companies."
That is a big reason why the team is extremely proud to receive this NIH grant.
"For us to get something like this is remarkable. 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," said van Horne.
Ball's experience with DBS-Plus is a beacon of hope for many battling Parkinson's disease. His journey underscores the importance of innovative treatments and the relentless pursuit of better outcomes for patients.
"I have absolutely no trouble. My quality of life is better than I could have ever hoped," said Ball. "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 renewed energy generated from NIH support, stories like Ball's emphasize the potential to change lives.
"When we turn off the stimulators, we see patients who are improved," said van Horne. "So, I think there's a lot of hope, and now is the chance for us to be able to prove that."
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG081356. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
