My reflections on studying Parkinson’s Disease

By Dr. Lucia Fernandez Cardo 

Edited by Sam & Chiara

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Parkinson’s disease (PD) owes its name to Doctor James Parkinson, who in 1817 described the disorder in his manuscript “An essay on the shaking palsy”. It has been 200 years since we began to study this disease, and despite the advances in understanding, we are still far from finding a cure.

PD is the second most common neurodegenerative disorder affecting 1-2% of the worldwide population. The pathological hallmark is the loss of dopaminergic neurons in a very small part of the brain called the Sustantia nigra, and the presence of protein depositions called Lewy bodies1. The loss of dopamine leads to a number of motor symptoms: bradykinesia (slowness of movement), rigidity, resting tremor, and postural instability. For the clinical diagnosis of PD, the patient must present bradykinesia plus one of the other three signs. Along with these motor signs, some non-motor symptoms are often present, amongst them anxiety, depression, dementia, sleeping disturbances, intestinal problems or hallucinations 2.

PD can be due to both genetic and environmental risk factors. 10-15% of the cases are described as familial PD with a clear genetic origin (mutations in SNCA, LRRK2 or Parkin genes are the main cause), the remaining cases are considered ‘sporadic’ or ‘idiopathic PD’ and are due to a possible combination of multiple genetic (risk polymorphisms) and environmental risk factors (toxins, exposure to pesticides, side effects of drugs, brain lesions, etc.)3-5.

In my experience, researching PD is something that I find challenging, but also motivational and rewarding. Every 11th of April (James Parkinson’s birthday), the regional and national associations of PD patients and their relatives have a day of celebration. They obviously do not celebrate having the disease, but celebrate being together in this battle and never giving up. This day they put aside the pain and the struggling, and celebrate that they are alive by gathering together, laughing, eating, and dancing.

When I was doing my PhD dissertation, I was lucky to be invited to this celebration as part of a group of scientists working on PD. Our group study the molecular genetics of PD, amongst other disorders, and my thesis was focused on studying genetic risk variants in sporadic patients. I will never forget how nervous I was, having to deliver a very brief talk, explaining the genetic component of PD and our current projects at the time. Some years later, though they may not remember me, I still clearly remember the smiling faces in the audience and the cheering and nice words that were said after I finished. Perhaps they did not grasp the most technical concepts, but for them, the mere fact of knowing that there were people researching their disease, working on understanding the mechanisms, and fighting to find a cure, was more than enough to garner many thanks and smiles.

Sadly, there is not yet a cure for PD, but medications, surgery, and physical treatment can provide relief to patients and improve their symptoms. The most common treatments (e.g.  levodopa, dopamine agonists, MAO-B inhibitors) all restore the dopamine levels in the brain 6. Levodopa is usually the most successful treatment but the side effects, appearance of dyskinesia (involuntary movement) and fluctuations in the effectiveness can be an issue with long term use. Some patients can be candidates for a very successful surgery treatment called Deep Brain Stimulation (DBS) which involves the implantation of a neurostimulator, usually in the top chest area, and a set of electrodes in specific parts of the brain. The electrical pulses stop the over excitation in the brain and the reduction of motor symptoms is astonishing. Follow the links below to check out some videos of the effects.

https://www.youtube.com/watch?v=wZZ4Vf3HinA https://www.youtube.com/watch?v=Uohp7luuwJI

Despite the treatments, these people can struggle daily due to the difficulty of finding the right drug combinations, the on and off phases of the medication, or the issues of carrying an internal battery to control the electrode pulses in their brain – and this is not even mentioning the possible non-motor symptoms of the disease. After spending a whole day with them I felt overwhelmed by their energy and good sense of humour and definitely saw things from a different perspective.

Finally, I just want to say that getting the chance to meet real people who have the disorder can be so important for us scientists. It helps to remind us why we dedicate so much of our lives researching a disorder. It is why during the hardest moments of failed experiments, struggling with new techniques, and so many extra hours of work, we can keep on going and will not give up. We do it so that we can see patients smile and keep up their hopes that we will one day find a cure for a disease as debilitating as PD.

 

 

REFERENCES

[1] Spillantini MGSchmidt MLLee VMTrojanowski JQJakes R and Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997 Aug 28; 388(6645):839-40.

[2] Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH and Deuschl G. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015 Oct; 30(12):1591-601.

[3] Lee A and Gilbert RM. Epidemiology of Parkinson Disease. Neurol Clin. 2016 Nov; 34(4):955-965.

[4] Billingsley KJ, Bandres-Ciga S, Saez-Atienzar S, Singleton AB. Genetic risk factors in Parkinson’s disease. Cell Tissue Res. 2018 Mar 13. [Epub ahead of print].

[5] Fleming SM. Mechanisms of Gene-Environment Interactions in Parkinson’s Disease. Curr Environ Health Rep. 2017 Jun; 4(2):192-199.

[6] Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, Coelho M and Sampaio C. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2018 Mar 23. [Epub ahead of print].

 

If you are interested in learning a little bit more about PD and helping us to demystify this disease, here is the link to some useful websites:

https://www.parkinsons.org.uk/

http://www.parkinson.org/understanding-parkinsons/

https://www.michaeljfox.org/understanding-parkinsons/index.html?navid=understanding-pd

 

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