June 19, 2019

expert reaction to study on early stage parkinson’s in the brain

Research published in Lancet Neurology analyses the propensity of people with the Ala53Thr gene mutation in developing Parkinson’s and the related early stage detection of Parkinson’s.

Dr Beckie Port, Research Manager, Parkinson’s UK, said:

“This is one of the first studies to suggest that changes in serotonin signalling may be an early consequence of Parkinson’s.

“Detecting changes that are happening in the brain in these early stages is a crucial gap in Parkinson’s research at the moment. Picking up on the condition earlier and being able to monitor its progression would aid the discovery of new and better treatments that could slow the loss of brain cells in Parkinson’s.

“Further research is needed to fully understand the importance of this discovery, but if it is able to unlock a tool to measure and monitor how Parkinson’s develops, it could change countless lives.”

Prof Derek Hill, Professor of Medical Imaging, University College London (UCL), said:

“Parkinson’s disease, like many other neurodegenerative diseases is thought to start years before a sufferer develops the characteristic “motor symptoms” of the disease.  And many experts think that treatment of Parkinson’s is most likely to be effective at the earliest possible stage, before symptoms are visible, often called “pre-motor disease”.   The twin challenges of developing such treatments are, firstly, how do you find people with “pre-motor disease”. And secondly, how do you evaluate whether a treatment of this pre-motor population is effective?   This research from King’s College London tries to help out with both of these challenges.

“The researchers found people with very early (pre-clinical) Parkinson’s disease by seeking out families in Greece and Italy with a very rare genetic mutation that makes them almost certain to develop Parkinson’s disease in their life time.  These people, unlike those with the much more common form of Parkinson’s disease which is largely due to bad luck, can be studied before they develop symptoms to help understand the biological course of the disease.  The researchers put these genetic mutation carriers, along with normal subjects and Parkinson’s’ patients, through a special type of brain scan that images the chemical messenger serotonin in the brain.   They found early changes in these brain scans in the parts of the brain known to develop hallmark Parkinson’s’ disease pathology later in the disease. The value of this research is that this serotonin imaging might both be a way of finding people who are in the earliest stages of Parkinson’s disease, and that the imaging might also provide a way of assessing whether a treatment for Parkinson’s’ helps slow down the progression of the disease if it is given before symptoms develop.

“This research provides some valuable insights into Parkinson’s disease. However, it has some important limitations. Firstly, they studied only 15 of the patients with a rare gene mutation. Their results may not scale up to larger studies. Secondly, the imaging method they used is highly specialised and limited to a very small number of research centres, so isn’t yet usable either to help diagnose patients or even to evaluate novel treatments in large clinical studies.  The research does, however, provide encouragement for the approach of trying to treat Parkinson’s Disease at the earliest possible stage, which is likely to be the best chance of preventing the rising number of people whose lives are destroyed by this hideous disease.”

Prof Tom Foltynie, Professor of Neurology, UCL, said:

 “This is a fascinating finding exploiting the fact that these individuals have either developed or are in a very high-risk group of developing Parkinson’s Disease (PD). At the moment, we are using the clinical symptoms- loss of sense of smell, constipation, depression and sleep disturbance as the first clues regarding the clinical onset of PD. It is tempting to speculate that the early loss of serotonergic neurons demonstrated in this study relates to some of the early features of PD particularly the sleep disturbances or mood disorder, but this needs to be more definitively established. How the more widespread loss of serotonergic neurons demonstrated later in the course of the illness relates to the clinical symptoms experienced by these patients also needs further study. As the authors point out, the major limitation is the current expense of performing DASB -PET imaging, and cheaper more available alternatives would likely be of great value to the PD research community”.

‘Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study’ by Heather Wilson et al. was published in Lancet Neurology at 23:30 UK time on Wednesday 19th June. 

Declared interests

Prof Derek Hill: No conflicts of interest

Prof Tom Foltynie: No conflicts of interest

None others received.