Precision Medicine
Original article: Espay, A. J., Brundin, P., & Lang, A. E. Precision medicine for disease modification in Parkinson disease. Nat Rev Neurol: 2017

The takeaway

Precision medicine aims to define and treat Parkinson’s by tailoring the right therapy to each person, depending not only on their specific signs and symptoms, but also on the specific molecular signatures of their disease.

Why is it important?

This is a new understanding of Parkinson’s, which moves us away from the concept of a single disorder, toward targeting the diverse molecular pathways underlying the unique condition and experience of each person with Parkinson’s.


Parkinson’s has been diagnosed clinically for decades, and managed with levodopa since 1967. Until recently, it was generally accepted that there is no cure, and research efforts focused on better drugs for symptom management. Only in the most recent years are important breakthroughs on neuroprotection slowly emerging. The hunt for disease modifying treatments for Parkinson’s is gathering momentum and important shifts are taking place in the minds of clinicians, researchers and patients. One potentially important development in this area refers to precision medicine: a more precise approach to defining, studying and treating Parkinson’s and targeting therapies to subgroups of patients based on their specific symptoms or molecular features of their disease. What does this mean in terms of a new understanding of Parkinson’s, and trials that may translate into radically new treatment approaches.

The details

Traditionally, Parkinson’s has been viewed as a single and “complex” disorder, with vast differences in signs (abnormalities discovered on clinical examination), symptoms (people’s experiences and reports) and the progression of the disease. Efforts to find different “subtypes” or subgroups have focused on superficial, visible patterns of how Parkinson’s manifests in different people: the tremor-dominant versus the tremor-free postural instability/gait difficulty subtypes, with their different links to cognitive impairment and dementia. Underlying this uneasy consensus is the view that there may be a single underlying process involving alpha-synuclein, shared by every person with Parkinson’s.

Similarly to other areas of medicine, recognition that cancer, for instance, was not a single disease led to massive progress in discovering the different, unique pathways underlying different subtypes. This now allows treating each individual with a unique regime, and targeting their disease precisely. A similar shift in the dominant view on Parkinson’s is now taking place, with leading clinicians and researchers around the world recognising that a ‘one size fits all’ approach it not serving us in the quest for cures. This is because each individual represents a unique profile of clinical characteristics (signs and symptoms), genetic and biochemical barkers. Rather than ignoring differences and trying to find a shared, common pattern across the millions of patient profiles that are routinely enrolled in trials and treated in clinic, the more constructive approach is to make meaningful sense of these differences. Using biomarkers, that is, biological substances, including genes, which allow us to identify and track disease, we are already discovering the different pathways that cause Parkinson’s in different people. This explains why one person can play numerous rounds of golf more than 20 years into their disease, while another may have significantly reduced mobility just 5 years after diagnosis.

Systematically addressing biomarker relationships to Parkinson’s, and focusing on different genes, inflammation profiles, glucose tolerance levels etc, will enable us to pinpoint a range of very different biochemical mechanisms, each leading to different forms of Parkinson’s. Espay et al describe this as a necessary “identity change” similar to the one that took place in oncology. Subtyping Parkinson’s on the basis of superficial signs and symptoms has not served the Parkinson’s community well. What we anticipate should be far more successful is subtyping according to different biomarkers that reveal different underlying disease processes.

Next steps

The better we are at characterising what makes each person’s Parkinson’s unique, the more streamlined their enrolment can be into trials of treatments that are most likely to be specifically beneficial for them.

The Parkinson’s community is recognising that progress on biomarker discovery is essential. This requires the collection and storage of biological samples (eg blood, CSF) for each patient enrolled in a trial, so that large numbers of these can be pooled and analysed now, or in the future. In addition, the development of a separate set of criteria for Parkinson’s which will now include biomarkers in addition to clinical signs will be informative, especially in clinical trials. Perhaps the most important next step in our hunt for cures may first be a step back before the next leap forward: with precision medicine, we need to redefine the different subtypes of Parkinson’s and target their diverse underlying processes with the right, tailored treatments.

Related work and trials


Where can I learn more?

Espay, A. J., Schwarzschild, M. A., Tanner, C. M., Fernandez, H. H., Simon, D. K., Leverenz, J. B., . . . Lang, A. E. (2017). Biomarker-driven phenotyping in Parkinson’s disease: A translational missing link in disease-modifying clinical trials. Mov Disord, 32(3), 319-324. doi:10.1002/mds.26913
Espay, A. J., Brundin, P., & Lang, A. E. (2017). Precision medicine for disease modification in Parkinson disease. Nat Rev Neurol, 13(2), 119-126. doi:10.1038/nrneurol.2016.196