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Early detection, treatment and the potential for future prevention is the precursor of a new era in Parkinson’s disease

Detecting Parkinson’s disease (PD) early is essential so that therapy may be given as early as possible to control symptoms and elicit any disease-modulating effects, said Professor Daniela Berg, University Hospital Tuebingen, Germany at the opening plenary session of the 2019 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held in Nice, France.

Clinical and research criteria for prodromal and early PD have been shown to work well, and an update of prodromal PD research criteria already exists. Professor Berg encouraged clinicians and scientists to apply the MDS clinical diagnostic criteria in routine clinical practice,1 and to apply the MDS criteria for clinically established early PD2 and the updated MDS research criteria for prodromal PD in clinical studies.3 More information on the MDS diagnostic criteria can be found on the article: Two centuries of struggle to define “a tedious and most distressing malady”

“Thanks to a joint effort we are getting better in detecting prodromal and early Parkinson’s disease”

Prodromal PD may be diagnosed through the identification of risk factors and prodromal markers, for which the MDS has established scientific criteria to calculate the probability of an individual being in the prodromal phase.4 In the 2019 update, new markers are identified that include diabetes, cognitive deficits, physical inactivity and low urate levels in men, along with revision to the likelihood ratio associated with established markers.3 A web-based PD risk calculator is now available that is easy to use, and Professor Berg urged clinicians to use it in their clinical practice.5

Clinicians are encouraged to use a new, web-based prodromal PD risk calculator in their routine practice

Starting treatment upon diagnosis or waiting until some functional disability develops are both valid approaches said Professor Shen-Yang Lim, University of Malaya, Kuala Lumpur, Malaysia and editorial board member of the Lundbeck Institute Campus, given that no proven neuroprotective effect is provided with current PD treatments.

 

The recent LEAP (Levodopa in Early Parkinson’s Disease) study showed that levodopa does not alter the disease course when given early -- the severity of PD symptoms did not differ significantly between patients who received early initiation of the drug and those who received delayed initiation -- which implies that levodopa has no disease-modifying effect on PD.6 Nonetheless, levodopa still has the best antiparkinsonian in early PD.7

Levodopa is not a disease modifying treatment for PD

Regarding which medication to use in early PD, Professor Lim advised that there is no “one size fits all”, and treatment needs to be individualized. Tailoring treatment to consider specific personal needs and the patient clinical phenotype is the basis of personalized medicine for PD today.8 Medication choice may be based on age, lifestyle, type and severity of motor symptoms, non-motor symptoms, comorbidities and patient preference.9,10

Tailoring treatment to consider specific personal needs and the patient clinical phenotype is the basis of personalized medicine for PD today

Professor Olivier Rascol, Toulouse University Hospital, France reviewed the evidence for disease-modifying treatment of PD, identifying that while there have been a lot of failures and disenchantments over the last 25 years, there are a lot of lessons learned from these previous “negative” steps, and a lot of promising new concepts and targets have reached early clinical development.11

 

Professor Rascol considered that a lot can be expected from research identifying subpopulations of patients sharing common Parkin-specific mechanisms that can be targeted by novel therapies. The discovery of genetic variants causing or increasing the risk for PD has provided potential therapies targeting α-synuclein, glucocerebrosidase (GBA1), and leucine-rich repeat kinase (LRRK2) that are now entering clinical trials.12

These herald the development of disease-modifying treatments based on knowledge of PD genetics and pathology. Ultimately, future research will establish biomarkers for prodromal PD with the potential for introducing disease-modifying therapy even before PD symptoms develop.13

The discovery of genetic variants causing or increasing the risk for PD heralds the development of disease-modifying treatments based on knowledge of PD genetics and pathology

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. Postuma RR et al. MDS Clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015;30(12):1591-601.

2. Berg D et al. Movement disorder society criteria for clinically established early Parkinson's disease. Mov Disord. 2018;33(10):1643-6.

3. Heinzel S et al. Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord. 2019;August 14 Epub: doi: 10.1002/mds.27802.

4. Berg D et al. MDS Research criteria for prodromal Parkinson’s disease. Mov Disord. 2015;30(12):1600-11.

5. Heinzel S et al. A web-based medical calculator for prodromal risk in Parkinsonism. Available from: https://www.movementdisorders.org/MDS/Journals/Other-Publications--Revie...

6. Verschuur CVM et al. Randomized delayed-start trial of levodopa in Parkinson’s disease. N Engl J Med. 2019;380:315-24.

7. Bressman S and Saunders-Pullman R. When to start levodopa therapy for Parkinson’s disease. N Engl J Med. 2019;380:389-90.

8. Titova N and Chaudhuri KR. Personalized medicine in Parkinson's disease: Time to be precise. Mov Disord. 2017;32(8):1147-54.

9. Fox SH et al. International Parkinson and Movement Disorders Society Evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2018;33(8):1248-66.

10. Lim SY et al. Integrating Patient Concerns into Parkinson's Disease Management. Curr Neurol Neurosci Rep. 2017;17(1):3.

11. Lang AE and Espay AJ. Disease modification in Parkinson’s disease: Current approaches, challenges, and future considerations. Mov Disord. 2018;33(5):660-77.

12. Sardi SP et al. Targeted therapies for Parkinson’s disease: From genetics to the clinic. Mov Disord. 2018;33(5):684-96.

13. Siderowf A and Lang AE. Premotor Parkinson's disease: concepts and definitions. Mov Disord. 2012;27(5):608-16.

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