A new study from King's College London upends conventional thinking about the origins of Parkinson's disease in the brain. The research reveals distinct changes in the brain's serotonin system can be identified up to 20 years before any Parkinson's symptoms appear, suggesting a new biomarker to detect the disease at its earliest stages.
Many devastating neurodegenerative diseases take years to develop before any direct symptoms become apparent. Parkinson's disease in particular is one neurodegenerative condition that some experts suggest would be more effectively treatable before symptoms are visible.
The big challenge for researchers has been in finding effective biomarkers that signal the disease in the its earliest pre-clinical stage. A large array of promising diagnostic methods have been floated in recent years, from blood and eye tests, to a remarkable recent study suggesting a smell secreted by the skin could signal the presence of the disease.
Parkinson's disease is generally thought of as a degenerative condition in the brain's dopamine system. This new research, however, set out to examine how the disease also affects the brain's serotonin systems. To identify whether this serotonergic system begins degenerating before symptoms appear, the researchers recruited a number of subjects carrying a very rare genetic mutation that makes them almost certain to develop the disease at a point in their life.
This genetic mutation is so incredibly rare the researchers suspect only around 100 people in the world currently carry it. These particular subjects presented as perfect case studies for investigating neurological biomarkers that may precede the visible onset of the disease. The new study spent two years tracking down 14 people with the mutation, then conducted comprehensive brain imaging to determine any neurological changes that preceded the onset of degenerative motor symptoms.
"We found that serotonin function was an excellent marker for how advanced Parkinson's disease has become," says first author on the study, Heather Wilson. "Crucially, we found detectable changes to the serotonin system among patients who were not yet diagnosed."
These changes to the serotonin system were found to precede any changes to the brain's dopamine system, suggesting this may be the earliest sign of the disease ever identified. The implications of the study are undeniably exciting, but Derek Hill, an expert in medical imaging from University College London, says there are a couple of significant limitations to the research that will need to be overcome.
"Firstly, they studied only 15 of the patients with a rare gene mutation. Their results may not scale up to larger studies," explains Hill, who did not work on this new study. "Secondly, the imaging method they used is highly specialized and limited to a very small number of research centers, so isn't yet usable either to help diagnose patients or even to evaluate novel treatments in large clinical studies."
The researchers readily admit the kind of PET scan used in the study is expensive and impossible to roll out as a broad clinical screening tool. The next step for the research, alongside verifying this serotonin system biomarker in larger cohorts, is to develop an affordable scanning technique that could be more widely deployed.
But perhaps more immediately the study offers substantial value to researchers working on new Parkinson's treatments. Tracking the degeneration of these serotonin systems in the brain could offer a novel way to monitor the efficacy of new drug treatments.
"Our results suggest that early detection of changes in the serotonin system could open doors to the development of new therapies to slow, and ultimately prevent, progression of Parkinson's disease," concludes chief investigator on the project, Marios Politis.
The new research was published in the journal The Lancet Neurology.
Source: King's College London
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