Biomarker hailed as “game changer” in Parkinson’s

UT Health's Claudio Soto

Claudio Soto of McGovern Medical School at UTHealth Houston, who is co-founder of Amprion

Researchers have discovered a new biomarker for Parkinson’s that could be used to identify people at risk of the disease and profoundly change the way it is treated.

The assay for a particular abnormal form of the protein alpha-synuclein – known as αSyn-SAA – could also be used to diagnose people with Parkinson’s more quickly, help identify the best treatment for patients, and speed up clinical trials of new therapies.

The test – which detects a misfolded form of alpha-synuclein – could eventually provide a far less-invasive alternative to a spinal tap, a painful procedure that is currently the only way to detect the protein.

A paper on the biomarker, published in the journal Lancet Neurology, found that αSyn-SAA was 87% accurate at detecting early-stage Parkinson’s disease in a cross-sectional analysis of 1,123 patients in the Parkinson’s Progression Markers Initiative (PPMI) cohort, recruited from neurology centres around the world.

Among participants who did not have Parkinson’s, the test showed the absence of the disease 96% of the time. Crucially, the study also revealed that 86% of prodromal or pre-symptomatic cases of Parkinson’s tested positive years before clinical symptoms of the disease appeared, opening the door for an early diagnosis before substantial damage in the brain.

Lead researcher Claudio Soto of McGovern Medical School at UTHealth Houston said the findings are “a game-changer” for people with Parkinson’s and will “contribute in a substantial way to understanding the pathogenesis of Parkinson’s, and the development of a much-needed therapy.”

Soto is the inventor of the seed amplification assay (SAA) technology used in the test, and also serves as chief scientific officer of biotech Amprion, which is developing a commercial version of the assay for early diagnosis of Parkinson’s.

Another interesting finding from the study was that 30% of participants with the LRRK2 gene mutation – which causes a disease with Parkinson-like symptoms – did not have misfolded alpha-synuclein, suggesting a different biological basis for their disease.

While the test currently needs to be carried out on cerebrospinal fluid harvested during a spinal tap, efforts are underway to see if the biomarker can be identified from a blood test, skin biopsy, or nasal swab.

The test has been developed with funding provided by the Michael J Fox Foundation (MJFF), which hailed the study as “the most significant breakthrough to date in the search for a Parkinson’s biomarker.”

“Validation of this biomarker launches a new, biological era in Parkinson’s research,” commented Kenneth Marek, principal Investigator of the PPMI, MJFF’s signature clinical study of Parkinson’s biology since 2010.

“This is what PPMI was built to do, and we are especially grateful to the thousands of study participants whose contributions have enabled this watershed moment,” he added.

The pharma industry is already taking aim at alpha-synuclein, designing drugs that target the protein in the hope of preventing its misfolding and formation into clumps that – a bit like amyloid in Alzheimer’s – are suspected of causing damage to neurons.

Roche and partner Prothena are currently thought to be the furthest ahead in the field, after starting a phase 2b trial of their prasinezumab candidate in patients with early-stage Parkinson’s, with regulatory filings expected sometime after 2025 if all goes to plan.