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Spotlight on Research Supported by PDF

Profile of Leo Verhagen, M.D., Ph.D.
Medical Director, Neurosurgery Program for Movement Disorders
RushUniversity, Chicago, IL

In 1999, Rush University Medical Center (RUMC) added significantly to an already impressive staff when it recruited Dr. Leo Verhagen to set up a surgical program for Parkinson’s disease and other movement disorders. Several projects in Dr. Verhagen’s surgical center — from the study of deep brain stimulation (DBS) to the potential role of gene therapy in treating Parkinson’s disease (PD) — are funded in part by the Parkinson’s Disease Foundation’s (PDF) annual grant to RUMC.

Within the movement disorder group at Rush, Dr. Verhagen directs all Parkinson’s surgery-related clinical and research activities. Dr. Verhagen has worked with Dr. Roy Bakay, a neurosurgeon, specializing in surgical treatment of movement disorders, to co-direct Rush’s surgery program since its creation. Through their collaboration, Rush plays a prominent role in the evaluation of several new, experimental surgical procedures for PD.

One of these is the implantation in the brain of cells from the retina that produce levodopa. This procedure was first performed by Dr. Bakay several years ago in six patients with excellent results and now is being evaluated in a large multi-center trial. Dr. Verhagen and his colleagues are also studying how DBS changes motor control to exert its beneficial effects, and what the impact of DBS is on cognition.

Perhaps the most exciting research project of the surgical center is one that began nearly a decade ago when investigators explored the possibility of treating parkinsonian monkeys with neurotrophic factors through gene therapy.  In this process, a gene that encodes a trophic factor for dopamine cells is inserted in a viral vector and the end-product is implanted in the brain.  Early results were reported in Science in 2002, showing how degenerating dopamine cells recover and start to produce dopamine again, leading to dramatic improvement in these monkeys.  

Modifications have been made since that time to make it possible to apply the same science that worked in monkeys to people. The newer technology applied to parkinsonian monkeys was reported in Annals of Neurology in 2006. In a nice example of how discoveries at the “bench” (laboratory) can be brought to the bedside, Dr. Verhagen’s team, in collaboration with a team at the University of California San Francisco, used this gene transfer strategy in an open-label clinical trial with humans in 2005.  So far the safety data are encouraging, and efficacy data, presented at this year’s annual meeting of the American Association of Neurological Surgeons, show a mean 36 percent improvement on a standard Parkinson’s disease rating scale.

This has led to a larger multi-center clinical trial that began in December 2006 (enrollment will be completed this fall).  Investigators are hoping that they will not only be able to provide symptomatic improvement for PD patients, but that — for the first time — they will also be able to protect dopamine-producing cells from further degeneration.

Dr. Verhagen’s work is supported as part of PDF’s matching grant to RUMC. During fiscal year 2008, PDF’s grant of $300,000 will be matched dollar-for-dollar by Rush’s own private fundraising, for a total of $600,000 in private funding.