Director, Laboratory of Molecular Neurosurgery
Dr. Kaplitt is an internationally recognized figure in the application of gene therapy to neurological disease. Gene therapy is the use of a gene to change the function of cells or organs to improve or prevent disease. Dr. Kaplitt was a pioneer in the application of this technique to the brain and nervous system. To transfer genes into cells, a small virus is used as a delivery package. This virus is rendered harmless, so that the package become like a "Trojan horse", delivering the gene into a target cell without spreading and without causing inflammation or disease. Recently, Dr. Kaplitt and his colleagues completed the first trial ever of gene therapy for Parkinson's disease. This was based upon concepts which have already proven to be successful in more traditional surgery, such as deep brain stimulation performed in Dr. Kaplitt's routine surgical practice. The surgical procedure was similar to the operation for deep brain stimulation, but rather than insert an electrode into a target deep in the brain, a gene was inserted to allow cells in that area to begin to make a particular chemical called a neurotransmitter. This was designed to re-establish the normal chemical balance which becomes dysfunctional in this area as well as elsewhere within circuits that controls movement. Studies in animals supported this concept, demonstrating both safety and long-term improvement in movements as well as in brain activity. Based upon this, a phase I trial was initiated in August, 2003, with the final of 12 patients treated in May, 2005. Since this was the first time that such a therapy was tried in human patients, surgery was only performed on one side of the brain. Therefore, patients were chosen whose symptoms were clearly worse on one side of their body. Patients are being followed for one year after surgery to determine the safety of the procedure, which is the primary goal of a phase I study. In order to plan for a larger study, however, patients are also being examined for severity of symptoms and brain scans are being performed to examine activity of affected areas. It has already been reported that there do not appear to be any toxicity related to the therapy at doses currently tested. The other measures are being evaluated, and a preliminary report of the available clinical and brain scan data was recently presented suggesting that there were significant improvements in both clinical measures and brain functioning. Since most patients with advanced Parkinson's disease have severe symptoms on both sides of their body, approval is currently being sought to expand the study to treat several patients on both sides of the brain, as is usually done with deep brain stimulation. If approved, it is anticipated that patients may be enrolled and treated in late fall of 2005 or early winter of 2006. Dr. Kaplitt also directs an active laboratory effort. The goal of this research is to better understand the reason that brain cells die in neurodegenerative disorders such as Parkinson's disease. Through this program, key pathways have been identified, and members of the laboratory are currently using this information to develop novel gene therapies to improve cell function and even stop cell death in experimental models of Parkinson's disease and Huntington's disease. The lab also has extensive collaborations with other leading researchers at Cornell and around the world to use gene therapy to better understand a variety of conditions, including complex pain, sexual dysfunction and obesity. Dr. Kaplitt is also involved in several clinical research studies. He is collaborating on studies examining the effect of deep brain stimulation on brain function in Parkinson's disease. He is also involved in a multi-center study investigating the potential for deep brain stimulation as a novel intervention for refractory epilepsy, and several patients have already been treated in this trial. Finally, he and his colleague Mark Souweidane are assisting Dr. Ronald Crystal in his trial testing gene therapy for Batten disease, an incurable pediatric neurogenetic disorder.