Understanding the different subtypes of Parkinson’s
Original article: The clinical heterogeneity of Parkinson’s disease and its therapeutic implications: European Journal of Neuroscience. 2018
Parkinson’s affects different people in many different ways. This review summarises the different ways in which progress has been in understanding these differences and identifying subtypes of Parkinson’s.
Why is it important?
Identifying different subtypes of Parkinson’s has important implications for how we decide on treatments now and how we might tailor clinical trials for the discovery of both symptom targeting and disease modifying therapies.
Although the medical definition holds that Parkinson’s is a movement disorder, we know this captures just a part of its effects. It is well recognized that Parkinson’s comes with motor, or movement related difficulties, as well as non-motor problems, which include wide ranging symptoms including, but only, fatigue, constipation and mood changes. Research efforts have focused on understanding how different symptoms might cluster together in different people, and tracing these back to specific changes in the brain, in order to help with management and understand this diverse condition better. The term used to describe these differences is “heterogeneity”, referring to the diversity in symptoms and their progression over time in different individuals.
First, efforts have focused on understanding differences in terms of symptoms. Generally, some people’s symptoms are more dominated by tremor, while others’ experience is characterized mainly by difficulties with posture and walking, with symptoms progressing at a faster rate. It has been suggested that people with the latter kind of difficulties also have more memory and thinking difficulties. While these two subtypes are best thought as two ends of a spectrum, many people may fall somewhere in between the two. Another approach has been to try to understand better what is going on at the level of neurons in different parts of the brain, and to develop a staging system on this basis. Again, this helps scientists to unpick where Parkinson’s may start in the brain, as well as understand interactions with the gut. Research into genetic approaches to Parkinson’s is ongoing, and many important mutations, or changes, have been identified. They include the gene for alpha synuclein SNCA, LRRK2 which is found in 1-3% of cases, GBA and others. Understanding how mutations in these genes cause Parkinson’s, and ways of translating this knowledge into developing new drugs is an area receiving a lot of attention.
Rather than working with people with Parkinson’s on a short term basis in the context of a trial or a study of limited duration, longitudinal studies whose aim is to study changes in people over several years have also revealed many useful insights. Data from these long term studies have helped further our understanding of the different rates at which some symptoms can change, and what the effects of different medications are on the disease course. Prognosis, that is, predicting the future for the individual with Parkinson’s is also extremely important, but the task is a difficult one. Rapid progress can be anticipated on this front thanks to a major international collaboration, the Critical Path for Parkinson’s Consortium, which is pooling data from different clinical trials and cohorts, attacking this important problem with as many data as possible.
By understanding the subtypes of Parkinson’s, and what is driving these potentially different mechanisms, it becomes possible to not only optimize treatments for symptoms, but also to match patients to clinical trials that are aiming at identifying drugs that can slow, stop or reverse the disease. A one size fits all approach simply will not do, so this fine tuning strategy is increasingly recognized as a research priority.
Original article: Greenland, JC, Williams-Gray, CH, Barker, RA: The clinical heterogeneity of Parkinson’s disease and its therapeutic implications. European Journal of Neuroscience. 2018