Welcome to Mathias Toft's project group
Our scientific interests are the causes and clinical presentation of Parkinson's disease and related disorders. We perform advanced genetic and genomic studies based on biological samples from patients and healthy individuals stored in a research biobank. We also study the clinical features of Parkinson's disease, in particular non-motor symptoms and symptoms associated with early-onset Parkinson's disease.
Our laboratory is localised in Domus medica 4, the newest building for medical research and education in Oslo (picture). Together with other researchers from the Department of Neurology we have formed the Neuroscience Research Unit. Clinical studies are performed in the adjacent hospital building.
Parkinson's disease is the most common neurodegenerative disorder second only to Alzheimer's disease. The disease presents clinically as a movement disorder characterized by tremor at rest, bradykinesia, rigidity and postural instability.
Neuropathological changes are loss of cells in the substantia nigra, normally accompanied by the formation of Lewy bodies and Lewy neuritis (Gelb et al. 1999). Typically, the onset of Parkinson's disease is insidious and steadily progressive as neuronal dysfunction and cell death lead to depletion of dopamine in components of the basal ganglia responsible for initiation and control of movement (Lees et al. 2009).
The neuropathology associated with PD progresses over time, and in more advanced stages lesions reach the cortex (Braak et al. 2003). In these stages many patients develop a range of non-motor symptoms in the form of sleep disorders, depression, gait and equilibrium difficulties, autonomic dysfunction and cognitive decline (Lang and Obeso 2004). This disease progression can currently not be influenced by available treatments.
The causes of Parkinson's disease remain largely unknown. A major breakthrough in recent years has been the identification of genes causing monogenic forms of the disease and genetic risk factors increasing disease risk (Pihlstrøm et al. 2013). Mendelian forms of PD are relatively rare and the genetic mutations only account for a small fraction of affected individuals. Nevertheless, the identification of proteins and pathways involved in the disease process has provided important information about the pathogenesis of the disease.
Current challenges are to identify further genetic and genomic factors involved in Parkinson's disease and to understand the molecular mechanisms predisposing to disease. Furthermore, by studying patients longitudinally our aim is to identify genetic and epigenetic factors influencing phenotypic variability, disease progression and severity.