In her thesis, neuroscience researcher Daniella Rylander presents two important findings that tackle different stages in the development of the uncontrollable jerky movements known as dyskinesia, which are an undesirable effect of treatment with the standard drug levodopa.
Dr Rylander has studied two different systems in the brain that are believed to play an important role in the development of the side effects – glutamate and serotonin. An overactivation of glutamate signals, caused by treatment with levodopa, probably contributes to the development of dyskinesia. Daniella Rylander’s research focuses on blocking this undesirable overactivation.
“The receptor cells have different receptors on their surface where the glutamate is taken in to activate the cell. It is these receptors that I have tried to block. If we could find the right channel and subdue it then we could get more effective treatment with levodopa without any side effects. This has always been my goal”, says Daniella Rylander.
Tests in animal models, including rats, have shown very good results for the new method. A drug that blocks glutamate overactivation via the glutamate receptor ‘mGluR5’ was used in the study. This has previously been tested on humans and so provides a head start in the time-consuming clinical trials required before a new drug can be introduced.
Serotonin also plays an important role in the development of dyskinesia in Parkinson’s disease.
“We have now shown for the first time that individuals who have a particularly large amount of a certain type of fibre on their serotonin cells are also at greater risk of being affected by dyskinesia after levodopa treatment”, says Daniella Rylander.
The new finding of a clear pathological change in the serotonin system can now be utilised to better tailor the individual treatment of patients with Parkinson’s disease.
Daniella Rylander, who is part of the Basal Ganglia Pathophysiology Unit research group, defended her PhD thesis on 17 September 2010. The thesis is entitled Involvement of non-dopaminergic systems in L-DOPA-induced dyskinesia.
Link to the Basal Ganglia Pathophysiology Unit research group: http://www.med.lu.se/english/expmed/research/basal_ganglia_pathophysiology