Over the past two decades, deep brain stimulation (DBS) therapy for patients with Parkinson’s disease (PD) has been extremely successful. It has been estimated that DBS has meaningfully helped tens of thousands of patients worldwide, improving tremor, dyskinesia, on-off fluctuations and several other Parkinson’s symptoms. DBS has however, fallen short in addressing disease progression issues including walking, talking and thinking. Scientists have long been enamored with the idea that since DBS is invasive, but relatively safe, it may be possible to use the guide tubes (straws that DBS leads are fed through to precisely place them into the brain) to deliver growth factors and other goodies to improve brain function. There is also evolving interest in developing DBS leads that could be connected to pumps. These pumps could continuously supply factors to the brain while maintaining the electrical current derived from the DBS device. In this month’s What’s Hot column we will introduce the concept of DBS plus.
The May 2016 edition of the Journal of Neurosurgery featured an article by Craig Van Horne and Greg Gerhardt from the University of Kentucky in Lexington. For many years, Craig and Greg have been interested in the delivery of neurotrophic factors as a strategy to restore or improve dopamine cell dysfunction in Parkinson’s. The experiment they devised was simple and clever. They used Schwann cells and neurotrophic factors within these cells from a superficial nerve (the sural nerve) in a patient’s own leg. The team then performed DBS, however before completing the operation they used the guide tubes to inject the nerve cells into the brain. They targeted the substantia nigra, one place where cells are known to die in Parkinson disease. Aside from three patients who reported a patch of numbness in the leg, there were no unexpected adverse reaction across all eight patients (Van Horne, 2016). The trial was registered at www.clinicaltrials.gov under NCT01833364. The investigators have now undertaken a second follow-up DBS study: NCT02369003.
This general procedure has been termed DBS plus. The idea of utilizing the DBS delivery system for neurotrophic and other factors is a novel idea. If such a procedure can be shown to improve effectiveness or to slow disease progression this could be an important advance for people with Parkinson’s. The idea of combination therapy for Parkinson’s disease (DBS plus) is something that experts should carefully consider for future trials. The synergy of DBS, medications, trophic factors, stem cells and other therapies may be a homerun for the next generation of therapies. Too often we try one therapy and quit. Another more promising direction may be to combine our field’s bright spots, such as DBS, with other promising therapies (Heath and Heath, 2010).
van Horne CG, Quintero JE, Gurwell JA, Wagner RP, Slevin JT, Gerhardt GA. Implantation of autologous peripheral nerve grafts into the substantia nigra of subjects with idiopathic Parkinson's disease treated with bilateral STN DBS: a report of safety and feasibility. J Neurosurg. 2016 May 6:1-8. [Epub ahead of print] PubMed PMID: 27153166.
Heath C and Heath D. Switch. Crown Business, 2010.
You can find out more about the Parkinson's Foundation National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease. You can read more from Dr. Okun in the What's Hot in PD? archives.