Parkinson's Disease Research Group
We are a multidisciplinary research group focusing specifically on Parkinson's disease (PD). Our research interests are two-fold:
1. To investigate the genetic causes of PD in the South African population and
2. To study molecular mechanisms leading to development of the disorder
PD is a debilitating and incurable neurodegenerative disorder that results from the loss of neurons in the substantia nigra. Once lost, these cells never grow back. This loss results in a number of symptoms which include resting tremor, rigidity (stiff muscles), bradykinesia (slow and limited movement and reflexes) and postural instability (difficulty with walking and balance). In addition to these symptoms, PD patients experience a number of psychological issues such as depression, psychosis, sleep disturbances and dementia.
Our group has shown that mutations in the known PD-causing genes are not common causes of the disorder in South African patients. However, a few pathogenic mutations have been found including one patient in whom we found a triplication of the entire SNCA gene (Keyser et al. Neurogenetics 2010). Currently, we are using next generation sequencing approaches, including whole exome sequencing and targeted requencing gene panels, to identify novel PD-causing genes in our patients.
Our work on dermal fibroblasts obtained from PD patients with mutations in the parkin gene has provided evidence for the involvement of mitochondrial dysfunction in the disease (van der Merwe et al. Biochem Biophys Res Commun 2014; Haylett et al. Parkinson's Dis 2016). Also, we have shown that the antioxidant curcumin (found in the curry spice turmeric) has potential therapeutic effects in a si-RNA mediated PINK1 knock-down model of PD (van der Merwe et al. Mol Neurobiol 2016). Studies are ongoing to examine the possible therapeutic effects of curcumin in various other cellular models of PD.
We started recruiting PD patients, family members and controls for genetic studies in 2008 and to date have collected and stored DNA samples from over 1,700 individuals (531 probands, 453 family members and 750 controls). Also, we have available dermal fibroblasts of patients (harbouring PD-causing mutations) and matched controls for functional studies. We have published our findings in various peer-reviewed scientific journals and have also written an invited chapter for the book entitled Parkinson's disease, 2nd edition, 2013 (Editors: Pfeiffer, Wszolek, and Ebadi).