4 biomarkers may point to early Parkinson’s disease: Study

Biomarker panel, clinical symptoms may help identify disease earlier

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A dropper hovers next to vials filled with blood.

A diagnostic panel of four biomarkers that combines the blood levels of a molecule called N-acetylputrescine (NAP) with three clinical features often present in Parkinson’s disease — loss of smell, depression, and acting out dreams — may help identify the disease at its earlier stages, a study found.

The study, led by researchers at BPGbio, showed that the four-biomarker panel performed better than each of the biomarkers alone to diagnose Parkinson’s, and was 20 times more likely to turn out positive if people had the disease than if they didn’t.

“A simple blood draw is a big step towards improving [Parkinson’s] diagnosis and making screening easier for clinicians and their patients,” Michael A. Kiebish, PhD, lead investigator and BPGbio’s vice president of platform and translational sciences, said in a company press release.

Kiebish said a timely diagnosis makes it possible for doctors to start “intervention in earlier stages of the disease,” when symptoms are fewer and often milder, and intervention is more likely to be effective.

The study, “Identification and validation of N-acetylputrescine in combination with non-canonical clinical features as a Parkinson’s disease biomarker panel,” was published in Scientific Reports.

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AI-developed panel of biomarkers for Parkinson’s disease

It’s difficult to diagnose Parkinson’s in its early stages, when motor symptoms haven’t yet developed. A timely diagnosis could mean better chances of treating the disease caused by the death of brain nerve cells (neurons) that produce dopamine, a chemical involved in motor control.

“There are currently no effective tools … to diagnose [Parkinson’s] before motor symptoms appear,” said Eric J. Nestler, MD, PhD, professor at the Icahn School of Medicine at Mount Sinai in New York and BPGbio’s scientific advisor. “This novel biomarker panel from BPGbio offers the potential to address this unmet need.”

The researchers already knew that NAP is present at higher levels in the cerebrospinal fluid — the liquid around the brain and spinal cord — of people with Parkinson’s than in healthy individuals. NAP results from the breakdown of putrescine, a polyamine.

Polyamines play a role in how cells grow, survive, or fight off stress, so their levels must be tightly regulated. In Parkinson’s, however, their levels are off balance, and cells that stock too many polyamines are more likely to grow toxic protein clumps, which can spread through the brain, causing dopamine-producing neurons to die.

The researchers used BPGbio’s artificial intelligence-driven platform to validate NAP as a blood biomarker for Parkinson’s and develop a diagnostic panel that combines the blood levels of NAP with early clinical features of the disease.

Blood samples from 194 people with Parkinson’s, with a mean age of 65.4, and 197 healthy individuals in the same age group were collected as part of the DISCOVERY-PD study (NCT02016092). Patients scored an average 2.1 points on the Hoehn and Yahr scale, indicating motor symptoms in both sides of the body without impairment of balance.

On average, the blood levels of NAP were significantly higher in people with Parkinson’s than in healthy individuals (4.74 vs. 3.7 ng/mL), consistent with earlier findings in the cerebrospinal fluid. There were no significant differences between men and women.

The cut-off value for distinguishing patients from healthy individuals was 6.91 pg/mL, with a sensitivity of 35% and a specificity of 90%. Here, sensitivity refers to how well NAP can diagnose Parkinson’s in people who have the disease, while specificity is the proportion of people correctly excluded from the diagnosis.

Of 121 clinical features analyzed, BPGbio’s platform identified those measured by the Brief Smell Identification Test (BSIT), the Hospital Anxiety and Depression Scale (HADS), and the Rapid Eye Movement Sleep Behavior Disorder Single-Question Screen (RBD1Q) as having potential diagnostic value.

Combining the blood levels of NAP with these three clinical features — loss of smell, depression, and acting out dreams — increased diagnostic accuracy compared with any of the four biomarkers alone, with a sensitivity of 52% and a specificity of 95%.

The four-biomarker panel was about 20 times more likely to be positive for people with Parkinson’s disease compared with those without the disease. In contrast, NAP alone had a much lower likelihood (4.79 times) of accurately identifying Parkinson’s.

“Results from this study demonstrated the power of a combined approach to [Parkinson’s] biomarker discovery along with the possibility of implementing NAP into clinical biomarker tests,” the researchers wrote.

The biomarker panel, which BPGbio has trademarked as parkinsonDx, is not yet available in the U.S. The company said it is looking into commercial partnerships.