Neurosurgeon Craig van Horne specializes in deep brain stimulation (DBS) to treat Parkinson’s Disease and other movement disorders. Recently, van Horne has melded ideas that were seeded at the Marine Biological Laboratory when he was an undergraduate with pilot studies on a possible way to slow or reverse the progression of the disease. His approach involves transplanting peripheral nerve tissue from the patient into their own brain during DBS surgery.

Parkinson’s Disease (PD) results from the progressive loss of dopamine-containing nerve cells in an area of the brain called the substantia nigra, and its symptoms and their severity correlate directly with this nerve cell loss. Motor symptoms include slowness of movement and, to varying degrees, rigidity, tremor and gait difficulty. The basis for selective loss of nerve cells underlying PD remains a mystery (see sidebar). 

Human brain and spinal cord nerve cells have limited capacity to regenerate after injury. In contrast, damage to the peripheral nervous system can result in regrowth of nerve cells and the return of function. Thus, the “milieu” of injured peripheral nerves is conducive to repair. 

Van Horne and his colleagues reasoned that placing segments of an injured peripheral nerve near nerve cells in the substantia nigra might result in neuroprotection and reduce deterioration and death. Their initial approach combined bilateral DBS surgery with unilateral transplantation of pieces of the patient’s peripheral sensory nerve (i.e., sural nerve) into the substantia nigra on the most affected side. 

They have found that their surgical procedure is both feasible and safe. A two-year clinical assessment of 14 patients has shown no significant worsening of gait and balance performance in 12 patients and an improved performance in two. Based on these positive results, the work has continued and is focused on transplantation to both sides of the brain with an increase in the volume of tissue delivered.

The preliminary results are encouraging and are very informative for designing a larger, randomized, double-blind, multi-institution clinical trial to test for true clinical efficacy. Van Horne hopes that their experimental approach has the potential to become part of PD therapy. 

Craig van Horne, on right, performing deep brain stimulation on a patient with Parkinson's Disease in 2023.
Craig van Horne, on right, performing deep brain stimulation on a patient with Parkinson's Disease in 2023. Photo courtesy of Craig Van Horne.

A Transformative Experience: Van Horne at the MBL

Before receiving his B.A. from Williams College in 1983 as a double major in biology and studio arts, van Horne decided to “taste” research in the spirit of his liberal arts experience in the laboratory of Prof. Steve Zottoli,  who at the time was studying regeneration of vertebrate neurons after injury. Van Horne spent part of the summer of 1982 at the Marine Biological Laboratory (MBL) with Zottoli, who is currently an adjunct senior scientist in the MBL’s Bell Center for Regenerative Biology and Tissue Engineering.

That summer, Albert Aguayo, a leader in neural regeneration research, gave the Grass Foundation’s Forbes lecture at MBL. Van Horne had a chance to meet with him to discuss his senior research proposal, and Aguayo generously took the time to conduct a few preliminary experiments with van Horne. This fortuitous connection with Aguayo in the collaborative environment of the MBL had a profound effect on van Horne. He acknowledged Aguayo’s contribution in his thesis by noting, “Special thanks goes to Dr. Albert Aguayo who helped to design and perform some of the operations while at the Grass Laboratory at Woods Hole during the summer of ’82. This thesis is in many ways a direct result from Dr. Aguayo’s previous research.”

Aguayo’s work in the late 1970s and early 1980s showed that central nervous system neurons that normally do not regenerate do so when exposed to the chemical milieu of a peripheral nerve. Van Horne focused on whether neurons in the central nervous system of goldfish could be induced to regrow in the presence of a nerve from the peripheral nervous system (i.e., the posterior lateral line nerve). Van Horne found that once sprouts of many injured axons contact the nerve implant, they elongate for distances greater than they would without the implant.

He and Zottoli published this work in abstract form in 1983. These experiments exposed van Horne to basic research, and the excitement of discovery. 

After graduation, van Horne wanted to continue the discovery process but was not sure how to choose a career path to do so. He entered the M.D. program in 1985 at the University of Colorado School of Medicine. The following year he transitioned into their M.D./Ph.D. program.

Craig van Horne.
Craig van Horne got his first taste of basic research at the MBL when he was an undergraduate at Williams College. Photo courtesy of Craig van Horne.

Van Horne joined Barry Hoffer’s laboratory, where he used neuro-transplantation in a rat model of Parkinson’s Disease. He continued in the Hoffer laboratory throughout the M.D. and Ph.D. portions of his training and determined that his career path necessitated combining neurosurgery and research with a focus on Parkinson’s Disease. To make this physician/scientist career a reality, he began a neurosurgical residency at Brigham and Women’s Hospital in Boston in 1992.

Van Horne returned to Williams College during his residency to share his passion for basic research and medicine with undergraduate students in a neurobiology course taught by Zottoli. One student who was fixated on the extended academic training van Horne needed to reach his goal asked, “When are you going to get a job?”  Van Horne paused, tilted his head, as if not understanding the question, and replied, “But I love what I do!”

After years of maintaining a laboratory that used a rat model of Parkinson’s Disease and performing deep brain stimulation surgery to treat PD at Brigham and Women’s Hospital and then Saint Elizabeth’s Hospital in Boston, van Horne moved to the University of Kentucky College of Medicine. The move to Kentucky resulted in the use of research concepts from his undergraduate and graduate years to treat Parkinson’s Disease.

By his own admission, van Horne had been thinking of combining peripheral nerve grafts with DBS in the treatment of PD for about 15 years before the current clinical trials. But the seeds for such an approach were planted by his fortuitous meeting with Albert Aguayo at the MBL in 1982 and research initiated at the MBL, which at the time had no bearing on human health and disease.

Craig van Horne, M.D., Ph.D. is currently the Virginia T. Barrow Endowed Chair at the University of Kentucky and a professor of neurosurgery in the University of Kentucky College of Medicine. He serves as co-director of the Brain Restoration Center, part of the Kentucky Neuroscience Institute. 

Steven J. Zottoli is Schow Professor of Biology, Emeritus, Williams College and adjunct senior scientist in the MBL’s Bell Center for Regenerative Biology and Tissue Engineering.

Selected References

Van Horne, C.G., J.E. Quintero, J.T. Slevin, et al. (2018) Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson’s disease during deep brain stimulation surgery: 1-year follow-up study of safety feasibility and clinical outcome. J. Neurosurg. 129: 1550-1561, DOI: 10.3171/2017.8.JNS163222

El Seblani, N., Welleford, A.S., Quintero, J.E., C.G. van Horne and G. A. Gerhardt (2020) Invited review: Utilizing peripheral nerve regenerative elements to repair damage in the CNS. J. Neurosci. Methods 335: 1-1, DOI: 10.1016/j.jneumeth.2020.108623

Chau, M.J., Quintero, J.E., Monje, P.V., Boss, S.R., Welleford, A.S., Gerhardt, G.A. and C.G. van Horne (2022) Using a transection paradigm to enhance the repair mechanisms of an investigational human cell therapy. Cell Transplantation 31: 1-13, DOI: 10.1177/09636897221123515

Parkinson’s Disease (PD) affects over 1 million individuals in the United States and 10 million worldwide. It is typically treated with the precursor to dopamine (levodopa) in combination with a decarboxylase inhibitor (Sinemet). The efficacy of this dopaminergic therapy can decline as the disease progresses, and unwanted motor movements may occur.  

A certain population of PD patients are candidates for deep brain stimulation. Under anesthesia, electrodes are lowered into the brain of a patient, using stereotaxic placement and electrophysiological characteristics of neuronal groups to locate specific areas of the basal ganglia. Once the targeted region is found, stimulation parameters can be adjusted to alleviate motor symptoms of the disease. A stimulator can be implanted under the skin, much like a pacemaker, to chronically provide the stimulation of the brain.

Neither the dopaminergic or DBS therapies slow the progression of PD. Craig van Horne and his colleague’s pilot studies are aimed at slowing or perhaps reversing the progression of the disease.