Basic Sciences and Translational Research
Dr. Stephen Pasternak oversees basic sciences and translational research. Dr. Pasternak’s research program is split between clinical research at CNARC/Parkwood Institute and a basic and translational science laboratory at the Robarts Research Institute at Western University.Basic Science
His laboratory at the Robarts Research Institute is focused on understanding the roles of subcellular compartments called endosomes and lysosomes on the production and clearance of beta-amyloid, a protein deposited in the brains of individuals with Alzheimer’s disease. Using live cell imaging, Confocal Microscopy, and Electron microscopy, he has discovered two brand new subcellular trafficking pathways that transport APP to the lysosome, one from the cell surface and one directly from the Golgi and is exploring mechanisms for amyloid secretion. Inhibiting APP trafficking in these pathways dramatically reduces Abeta production, suggesting these transport events may be a new therapeutic target in Alzheimer’s disease.
Translational Research
Currently there are no good techniques to diagnose Neurological disease. Dr. Pasternak is collaborating with Dr. Robert Bartha (Robarts Imaging/UWO) and Dr. Robert Hudson (Department of Chemistry, UWO) to develop contrast agents for non-invasive detection of enzyme activity in live individuals. We are currently focused on lysosomal enzymes such as Cathepsin D which are highly elevated in neurons, amyloid plaques, and CSF of Alzheimer’s disease patients. A radiolabeled PET version of this agent is able to identify Alzheimer’s disease transgenic mice. A PET version of this agent targeting the enzyme Caspase 3, which is involved in Apoptosis (programmed cell death), appears to be able to identify cells undergoing cell death.
Clinical Research
Currently all of the treatments for Parkinson’s disease treat the symptoms of the disease, but do not change the long-term course of pathology in the brain. At CNARC/ Parkwood Institute, Dr. Pasternak is running an Investigator-Initiated Phase 2 clinical trial of Ambroxol as a disease modifying drug for Parkinson’s disease Dementia. Parkinson’s disease is cause by the accumulation of a protein called alpha synuclein in the brain. Ambroxol is an over the counter cough medicine, which is available in much of the world, but not available in Canada or the USA. Ambroxol is pharmacological chaperone of a lysosomal enzyme called GCase, which is linked to alpha-synuclein. In cells and animal models, raising the levels of GCase is known to reduce the levels alpha-synuclein, the pathological proteins that deposit in the brain in Parkinson’s disease. Our goal is to randomize 75 patients with Parkinson’s Disease Dementia for 1 year and to follow them with cognitive and motor testing.
Current Projects
If you would like more information please contact our Research Coordinator, Sarah Jesso
519.646.6000 x64852
Sarah.Jesso@sjhc.london.on.ca.
