Weill Cornell Medicine Neurological Surgery has led the development and testing of gene therapies for Parkinson's disease. As a PhD student 30 years ago, Dr. Kaplitt developed the technology for safe, efficient delivery of genes to the brain. As a junior faculty member in 2003, Dr. Kaplitt became the first person in the world to treat a human patient with gene therapy for Parkinson’s disease. He then helped to design and lead a second trial that to date remains the only study of gene therapy for Parkinson’s disease to meet the primary study goals when compared to a group of patients receiving sham surgery. This video explains this gene therapy process:
Dr. Kaplitt has also worked closely with Dr. Ronald Crystal, Chair of Genetic Medicine at Weill Cornell Medicine and a gene therapy pioneer, on gene therapies for developmental brain disorders and for Alzheimer’s disease. The Laboratory of Molecular Neurosurgery within Weill Cornell Medicine Neurological Surgery is also actively researching novel methods for understanding and treating a variety of unmet needs in Parkinson’s disease treatment, including levodopa-induced dyskinesia, sleep and swallowing disorders in Parkinson’s disease, and weight disorders, as well as cognition and depression. An active research area is also examining the emerging role of the gut-brain axis in Parkinson’s disease, in order to understand how pathology may spread from the gut to the brain to cause Parkinson’s disease and how we may use non-invasive genetic interventions to prevent this spread. Finally, methods to protect at-risk brain cells from death as well as methods to create new brain cells to replace the lost neurons in Parkinson’s disease are both under study.
There are currently three clinical trials of gene therapy for neurodegenerative disorders underway at Weill Cornell Medicine Neurological Surgery. (All three are in the stage where patients who participated are being monitored; none is open to new participants at this time.) One is a trial of gene therapy for Parkinson’s disease patients with mutations in the gene for glucocerebrosidase, a gene that has been associated with certain forms of Parkinson’s disease and may be the most common genetic cause of this disorder. The goal is to insert a normal copy of the gene into brain cells widely throughout the brain, in order to restore a more normal level of enzyme product of this gene and thereby slow progression of the disease in such patients. Another trial is gene therapy for Alzheimer’s disease patients through wide delivery of the gene for ApoE2. This has been associated with protection from Alzheimer’s disease pathology, while those who have two copies of the ApoE3 gene or one copy of the ApoE4 gene are at greater risk for disease. The goal of this ongoing study is to deliver the ApoE2 gene to patients who lack any copies of this form of ApoE to slow progression of this disease. The third is the most recent study of AAV-GAD gene therapy in the subthalamic nucleus, originally developed by our department, which aims to restore more normal circuitry to improve symptoms of patients with Parkinson’s disease.
Reviewed by Michael Kaplitt, MD, PhD
Last reviewed/last updated: July 2024
