11th of November 2018
In trying to explain why I got Parkinson’s I often see myself using the metaphor of a bingo card. You must have scored in a number of boxes to win the Parkinson bingo. And, well, I just did.
I find the image of a bingo card supported in a paper released in Trends in Neurosciences (1). The authors believe that the factors that lead to Parkinson’s can be divided into three categories:
Years before Parkinson’s becomes visible, triggers mark the beginning of a cascade of events. Think of inhaling a trigger pathogen that – after swallowing – reaches the intestines (2,3). Most people never develop Parkinson’s disease because they do not have ‘facilitators’ and ‘aggrevators’.
If triggers are the spark, facilitators fan the flames, says Benjamin Stecher in his blog (4). An example: In order to defend itself against the pathogen, the production of the protein alpha-synuclein is initiated in the intestines (5). But something goes wrong. Too much is produced, the protein folds incorrectly, it transports to the brain.
If the misfolded alpha-synuclein accumulates in the brain and isn’t cleaned up because the removal mechanism falters (disturbed autophagy) then you have an ‘aggravator’ at hand. A combination of triggers, facilitators and aggravators leads to the eventual death of the dopamine-producing neurons in the substantia nigra.
You don’t have to be a mathematical genius to see that a lot of different combinations can hit the jackpot. According to the authors this image is illustrative for the fact that Parkinson’s dresses up in so many different costumes. Parkinson’s isn’t a single disease. No one Parkinson’s patient has the exact same symptoms. What they do have in common is that they will loose dopamine producing neurons as time progresses.
The vast array of different combinations of factors in these three categories can explain some of the clinical variability observed in patients with PD, including their symptomology, rate of progression, and response to treatments (1).
Why is this work important?
This work is important in three ways:
- It helps to develop the discussion on subtypes of Parkinson’s further;
- It helps to reconsider why some clinical studies failed. Parkinson’s patients which have already developed serious symptoms, may be past the phase where they can be cured with medication which focuses on an earlier event in time (where triggers and facilitators were active);
- It makes evident the importance of intensifying the search for biomarkers (Parkinson’s predictors) for the early stages of Parkinson’s.
Why is this work important to me?
For me, the personal relevance is that – in this model – I feel acknowledged in the uniqueness of my disease pattern.
What I often see, is that Parkinson patients are statistically divided, e.g.:
- More men than women have Parkinson’s;
- On average, Parkinson starts at the age of 6o years;
- Individuals with a highly creative artistic occupation have a reduced risk of Parkinson’s (6).
But, the individual is always lost in statistics. I am a very creative woman (by profession) from 49, so you see my point ; -)
But most important, I do not yet see how such statements further the discussion on Parkinson’s and how they help in finding a cure to prevent neurodegeneration.
Maybe I will learn to think different about this issue as time passes, but for now I am very grateful for the Parkinson bingo model of my disease.
(1) Johnson, M. E. , Stecher, B. , Labrie, V., Brundin, L., Brundin, P., (2018), Triggers, Facilitators, and Aggravators: Redefining Parkinson’s Disease Pathogenesis, Trends in Neurosciences, Retrieved from https://doi.org/10.1016/j.tins.2018.09.007
(2) Braak H., Del Tredici K., Rüb U., de Vos R.A.I., Steur E.N.H.J, Braak E. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211. https://doi.org/10.1016/S0197-4580(02)00065-9
(3) Rietdijk, C. D., Perez-Pardo, P., Garssen, J., van Wezel, R. J., & Kraneveld, A. D. (2017). Exploring Braak’s Hypothesis of Parkinson’s Disease. Frontiers in neurology, 8, 37. Retrieved from https://doi:10.3389/fneur.2017.00037
(4) Stecher, B., (2018, October 24), Triggers, Facilitators and Aggravators: A New Hypothesis of Parkinson’s disease, [Blog post], Retrieved from https://tmrwedition.com/2018/10/24/triggers-facilitators-and-aggravators-a-new-hypothesis-of-parkinsons-disease/
(5) Emamzadeh F. N. (2016). Alpha-synuclein structure, functions, and interactions. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 21, 29. Retrieved from https://doi.org/10.4103/1735-1995.181989
(6) Darweesh, S. K. L. , Ikram, M. K., Faber, M. J. , de Vries, N. M., Haaxma, C. A, Hofman, A., Koudstaal P. J., Bloem, B.R, Ikram, M. A. (2018), Professional occupation and the risk of Parkinson’s disease. European Journal of Neurology Volume 25, Issue 12, Retrieved from https://doi.org/10.1111/ene.13752