NEW Research - Is Parkinson's Genetic?? - Penetrance of Parkinson's Disease in LRRK2 Carriers Is Modified by a Polygenic Risk Score.

Here is a nice paper by colleagues from the International PD Genomics Consortium (IPDGC)...
https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27974

One question I frequently get asked is "doctor, please tell me, is it genetic?"... I am instantly caught in conflict between offering swift reassurance because I know what people really mean is "will I pass this on to my children?" OR a providing a rather convoluted explanation along the lines of 'yes in some ways Parkinson's is genetic but because of a whole range of genetic factors affect one's risk of getting Parkinson's just a little bit'.

The truth is that most complex diseases are genetically determined to some extent and Parkinson's is a good example. That doesn't mean that if you have Parkinson's your relatives will definitely also get Parkinson's, but they might be at slightly higher risk. The strength of the genetic factors that they have and the combination of factors adjust the overall risk in individuals. 

This offering from the IPDGC is an example of how different genetic factors combine... 

LRRK2 is the commonest genetic cause of Parkinson's that we know about. Having a mutation in LRRK2 causes Parkinson's in about 30% of carriers in their later years. These mutations have a 50% chance of being passed on to the next generation, who then in turn also have about 30% chance of showing signs of Parkinson's in their later years. What determines the chance of showing signs of Parkinson's? Well at least in part it is likely due to the other genetic risk factors that you have. 

In this paper, the authors show that having other genetic risk factors for Parkinson's (combined in a score) affects how likely carriers of LRRK2 mutations are to show signs of Parkinson's and that on average they tend to show them earlier in life. 

Why is this important? LRRK2 drugs are being tested to see how they might protect people carrying mutations of LRRK2 against getting Parkinson's. It is likely that the combination of other genetic factors that people have will help select groups for trials and might also affect the response to treatment. This kind of research gets a little bit closer to realistic precision medicine for Parkinson's 

Alastair Noyce

NEW Research - Motor complications in Parkinson's disease: 13‐year follow‐up of the CamPaIGN cohort

Back on the blog for the first time in a long time...

This marks another NY resolution to speak and flag more about the research that I/we think is interesting or important in the early identification or prediction of PD. In addition, we like to mention good quality clinical and genetic studies that tell us more about PD in general (not just prediction and early identification). 

First off, the latest from the CAMPAIGN study. CAMPAIGN is one of the most rigorous and thorough long term studies of PD. The team have managed to follow up the people that they recruited with PD for a long, long time in order to help us learn more about the features that emerge over time.

In the present study, they show that eventually motor complications may be inevitable and that current drugs become less effective/predictable over time. Importantly they provide further support for the notion that levodopa replacement itself is not a cause of motor fluctuations and that thoughts about saving levodopa for the future (i.e. not starting after diagnosis) are probably outdated ideas.

Ultimately, whilst the available treatment options are good for most patients, the results here support our ongoing desire to find drugs that delay progression rather than just manage the symptoms...

The link to the study is here and it is open access (👌). The abstract is copied below.
https://onlinelibrary.wiley.com/doi/full/10.1002/mds.27882

Alastair Noyce