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Dr Victor Dieriks

Finally, some good news about Parkinson’s disease

Patients suffering from Parkinson's disease symptoms can experience hand tremors. Photo: Getty Images

Researchers publish good news in the quest to improve diagnosis and treatment of Parkinson's disease, writes Dr Victor Dieriks

In a significant advancement in understanding Parkinson's disease, researchers have discovered a new tool that can detect abnormal α-synuclein, the major pathological protein in Parkinson’s disease.

The breakthrough, announced in The Lancet Neurology May issue, opens up new possibilities for research and treatment. People with Parkinson's can expect faster care and improved treatments, and newly diagnosed individuals may never advance to full-blown symptoms.

These prospects cannot come soon enough. From 1990 to 2015, the number of people with Parkinson’s disease more than doubled from 2.6 million to 6.3 million. Currently, 10 million people are estimated to have Parkinson’s disease, 12,000 of whom live in New Zealand, with numbers steadily rising year-on-year. The old-school thinking that Parkinson’s disease only affects older people is no longer accurate, with many people now being diagnosed in their 30s and 40s. Even teenagers, although rare, get diagnosed with Parkinson’s.

Researchers have developed a new ground-breaking test to detect abnormal α-synuclein in brain and body cells. This protein is normally found in the nervous system, but in Parkinson’s disease, it misfolds and clumps, damaging neurons. Up to now, it was only possible to confirm the presence of these clumps through post-mortem analysis.

The α-synuclein seed amplification assay (ASA) investigated by the researchers in The Lancet Neurology paper marks a significant milestone in finding better treatments and a potential cure for Parkinson’s disease, and establishes an entirely new chapter of research.

This newly validated test can accurately detect pathology in spinal fluid not only in people diagnosed with Parkinson’s disease but also in individuals who have not yet been diagnosed or shown clinical symptoms of the disease but are at a high risk of developing it.

With this novel, early diagnostic capability, it is possible that individuals may never advance to full-blown symptoms, and everyone living with Parkinson’s can in the long run expect earlier care and improved treatments. We already know that early intervention has a massive impact on patient outcomes, so starting treatment, particularly therapeutic interventions, years before the typical tremor, shaking, and changes in mood and balance start would be an absolute game changer.

The α-synuclein seeding amplification assay test exploits an inherent characteristic of α-synuclein, whereby existing clumps recruit nearby normal – ‘unclumped’ – α-synuclein to misfold, triggering a snowball effect. For the assay, spinal fluid samples are prepared with a fluorescing dye that only lights up if α-synuclein clumps form, thereby permitting the selective detection of pathological α-synuclein. If no abnormal α-synuclein is present, the dye doesn’t fluoresce.

After previously being tested in small, independent studies, the assay was validated in the large, well-characterised cohort of the Parkinson’s Progression Markers Initiative (PPMI). The validation was executed by an international coalition of scientists led by the Michael J. Fox Foundation. The study published in Lancet Neurology tested 1,123 samples of spinal fluid contributed by PPMI participants over the years. The assay returned data with amazingly high accuracy, with 93 percent of participants with Parkinson’s having an abnormal test. Very few tests for neurologic disorders are over 90 percent sensitive.

Further development of the α-synuclein seeding amplification assay test will accelerate its widespread and standard use. The test currently elicits a yes/no result — showing that abnormal synuclein is either present or not, but there is tremendous promise in optimising it.

Further developments will allow measuring the amount of α-synuclein present and enable diagnosis of multiple system atrophy (MSA), a condition often misdiagnosed as Parkinson’s disease. Getting the diagnosis right from the start would mean that patients get the correct therapy from the beginning.

My group at the University of Auckland is researching how to use this test widely without needing spinal fluid; extracting spinal fluid still involves an invasive technique. Instead, future assays would enable us to detect abnormal α-synuclein in blood, nasal swabs and urine samples — a simple sample that could be collected in any GP’s office.

With this discovery, Parkinson’s disease is moving from a disease primarily diagnosed when the motor symptoms become visible and measured through subjective clinical assessments to an objectively biologically defined disease. This brings earlier diagnosis, targeted treatments, and faster and cheaper drug development much closer. There’s an exciting future ahead. The prospects of cracking down on Parkinson’s disease have never looked better.

Dr Victor Dieriks, is Group leader of the Synuclein group at the University of Auckland. His group is part of the global effort to further develop and optimise this α-synuclein seeding amplification assay test. Find out more at Dierikslab.com.

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