Alzheimer’s and Parkinson’s disease are progressive neurodegenerative diseases for which no treatment is currently available. My group investigates the processes that underlie the neurodegenerative processes. One mechanism is the failure of growth factor signaling. We are testing a range of growth-factor like peptides that originally have been developed to treat type 2 diabetes. These peptides show neuroprotective effects in cell culture and in mouse models of Alzheimer’s and Parkinson’s disease. One of these peptides that is on the market to treat type 2 diabetes is currently in a clinical trial in Alzheimer’s patients.

• Cell culture studies to investigate the protective effects of novel analogues of GLP-1 and GIP peptides. Cell survival, oxidative stress and apoptosis is tested, and the secondary cell signaling pathways linked to growth factors are analysed
• Animal models of Alzheimer’s disease are tested for memory loss and synaptic impairment of transmission, for the chronic inflammation response, for amyloid plaque development in the brain and synaptic loss
• Animal models of Parkinson’s are used to investigate the effects of novel drugs in preventing MPTP or 6-OHDA lesions that induce Parkinson like symptoms. Cell survival in the brain and dopamine synthesis are analysed
• Coordinating clinical trials in Alzheimer’s patients at the Hammersmith hospital in London with Imperial College, in Parkinson’s patients at the Cedars-Sinai hospital in Los Angeles and at the Shanxi Medical University hospital in Taiyuan, China

My research is focused on neurophysiological and pathophysiological processes in the brain.

The main focus of research of my group is to analyse the processes in neurons that underlie Alzheimer’s disease. Techniques employed include work with transgenic mice that express human mutated APP/PS1 proteins, in vivo electrophysiology, behavioural testing, histology, biochemical analysis of protein expression, and cell culture work. A second branch of research is the analysis of cellular process in the development of Parkinson’s disease. In transgenic mice that express the human mutated alpha-synuclein protein and in other animal models are used that have chemical lesions of the substantia nigra and display Parkinson symptoms. Behavioural and histological analyses are conducted to evaluate the protective effects of novel drugs on neurons in the substantia nigra, dopamine production and on motor activity.  

A main research topic is on the recently described connection between type 2 diabetes and Alzheimer’s and Parkinson’s disease is under investigation, and several novel GLP-1 incretin analogues developed to treat type 2 diabetes have shown impressive effects in reducing degenerative symptoms in animal models of Alzheimer’s disease and Parkinson’s disease. These mouse models recapitulate aspects of the human disease, such as the expression of human mutated amyloid precursor protein, presenilin-1, and tau protein. Currently, collaborations with several Pharmaceutical companies are in progress to evaluate novel compounds that hold promise in the treatment of neurodegenerative conditions. A clinical trial to test the GLP-1 analogue liraglutide in Alzheimer patients has started. This trial takes place at the Hammersmith research hospital in London, in collaboration with Imperial College. Several clinical trials testing liraglutide in Parkinson’s patients are in planning. These are supported by the Cure Parkinson’s Trust, and the Cedars-Sinai hospital in Los Angeles. In addition, a trial is in planning at the Shanxi medical university hospital in Taiyuan, China. Initial preclinical research at that hospital is supported by funds of the Chinese government.