A good marker

How biomarkers are shaping Parkinson’s diagnosis and clinical trials

An estimated 10 million people worldwide live with Parkinson’s disease – a progressive neurodegenerative disorder that primarily affects dopamine-producing neurons in a specific area of the brain called the substantia nigra and reduces the brain’s ability to control movement and balance.

Since the 1980s, the number of people diagnosed with Parkinson’s has steadily increased, with a marked acceleration in the past two decades partly attributed to an ageing population worldwide, as the disease predominantly affects older adults.
While the exact cause of Parkinson’s remains unclear, researchers have identified several biological processes and molecular indicators that may contribute to its onset.

These indicators, known as ‘biomarkers’ – which include proteins, chemicals and other molecules that indicate normal or abnormal processes in the body – are becoming an increasingly powerful tool in the early detection of numerous conditions including various cancers, as well as liver and heart diseases.

In a recent study, researchers identified a biomarker in spinal fluid with the potential to detect Parkinson’s disease in its early stages with over 90% accuracy. This includes the misfolding and clumping together of the alpha-synuclein (αSyn) proteins in the brain, which interfere with brain function; excess iron build-up in the brain; and chronic inflammation triggered by an overactive immune response in the brain.

This discovery represents not only a step forward in the ongoing effort to improve early diagnosis of Parkinson’s, but also an indication that biomarkers may hold answers to some of our most pressing pathological questions.

As such, continued research on reliable biomarkers may offer new pathways for early diagnosis, more targeted and personalised treatments, and faster, more effective clinical trials ultimately transforming how Parkinson’s and similar diseases are managed.

Because there is no definitive test for Parkinson’s disease, physicians typically rely on a combination of physical and neurological evaluations – cognitive testing, coordination assessments, imaging scans – as well as genetic testing to identify indicative symptoms.

Without conclusive screening or testing options, patients with early onset Parkinson’s disease often do not meet the clinical diagnosis criteria until well after fine motor skill symptoms have clearly manifested.

By that point, approximately 60-80% of dopamine-producing neurons have already been lost, and the brain will have already been severely and irreparably damaged.  Parkinson’s symptoms also share similarities with other disorders, such as dementia with Lewy bodies, multiple system atrophy and corticobasal syndrome, further complicating early and accurate diagnosis.

The long-standing uncertainty around Parkinson’s disease progression and diagnosis is exactly why recent discoveries regarding the role of biomarkers like the αSyn protein in Parkinson’s development are especially noteworthy.

betaSENSE, a new diagnostic technology that uses immune-infrared sensors, has proven effective in detecting the sticky, toxic deposits that form in the brain when αSyn proteins become misfolded.

It builds on previous success in Alzheimer’s detection, where the same tool was shown to predict the onset of dementia up to 17 years before outward symptoms appeared.

In 2024, the FDA released a “Letter of Support”: ‘encouraging drug developers to continue to explore the use of the αSyn biomarker in research and clinical trials’.

αSyn is just the beginning. Ongoing research has already uncovered a growing number of other biomarkers that can aid not only in early Parkinson’s diagnosis, but in tracking the disease as it progresses.

For instance, the advanced imaging technology FMT-PET allows for high-resolution tracking of AADC enzyme variations and activity over time, giving researchers a window into how Parkinson’s affects neurotransmitter production – like dopamine – in the brain.

In one study, patients with REM sleep behaviour disorder – a known risk factor for Parkinson’s – showed significantly reduced AADC levels on follow-up scans, suggesting early neurochemical changes well before obvious motor symptoms appeared.

These insights not only enhance understanding of how the disease develops but also create opportunities for earlier interventions that could potentially slow or halt its progression.

Consequently, biomarker research is paving the way for more targeted clinical trials for Parkinson’s treatment. The impact of biomarkers on clinical research can be seen in the following domains:

• Patient stratification: Biomarkers help clinical researchers identify specific genetic mutations like LRRK2, which influence the abnormal accumulation of the αSyn protein. This targeted approach is crucial in clinical trials, as it ensures that therapies are tested on the most relevant patient populations, leading to more meaningful results and potentially accelerating the development of effective treatments
• Target validation: Biomarkers are also applied in experimental therapies to study if they are able to hit their intended molecular targets and mechanisms of action. One clinical trial using the immunotherapy PD03A demonstrated results in slowing the misfolding of the αSyn protein, which occurs before more dire Parkinson’s symptoms appear
• Safety monitoring: Another clinical trial recorded that the use of the medication nilotinib at 150 and 300mg had no biomarker benefit and ultimately worsened motor scores for patients with Parkinson’s. Based on this evidence, the trial authors had sufficient data to decide to cease use of treatment on the patients, thus preventing incidents of adverse events and upholding the safety of the study.

By enabling earlier diagnosis, more accurate tracking of disease progression, and more targeted, effective drug development, the discovery of reliable biomarkers for Parkinson’s marks a turning point in the fight against this fatal condition.

For the millions affected by this disease – and the millions more at risk – these advancements may offer earlier interventions, better patient outcomes, and hopefully, a future where Parkinson’s is a manageable condition.