Levels of Progranulin Protein May Affect Parkinson’s Severity, Progression

Blood levels of progranulin — a protein whose deficiency has been linked to neurodegeneration — may reflect Parkinson’s severity and progression, and serve as a disease biomarker, a recent study suggested.

The research, “Reduced plasma progranulin levels are associated with the severity of Parkinson’s disease,” was published in Neuroscience Letters.

Progranulin is widely distributed throughout the brain. Studies indicate this protein is a potent regulator of neuroinflammation and a promotor of long-term neuronal survival.

Low progranulin levels have been associated with neurodegenerative and lysosomal storage disorders. Blood levels of progranulin are also suggested to be lower than usual in Parkinson’s patients.

But little is known about how blood levels of progranulin and disease severity in Parkinson’s might correlate.

Researchers explored this possibility by measuring progranulin blood concentrations and correlating them with symptom severity.

Their study involved 55 patients (24 men and 31 women, mean age 71.1) and 55 people without the disease serving as controls, (22 men and 33 women, mean age 67.8).

Disease severity was quantified using the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale. Patients’ motor symptoms were assessed using the UPDRS motor section (UPDRS-III).

Blood plasma tests revealed that progranulin levels were significantly lower in Parkinson’s patients compared to controls (333.8 vs. 364.2 ng/ml). Blood levels of progranulin were also found to negatively correlate with Parkinson’s severity, motor symptoms, and disease duration.

This means that lower progranulin levels associated with greater disease severity and motor symptoms, and longer disease duration. It also indicates a possible protective role of progranulin against the neurodegeneration process associated with Parkinson’s.

Previous studies have shown that boosting progranulin production protected dopamine-producing neurons from degeneration in mouse models of Parkinson’s, supporting progranulin’s role in better neuronal survival and neuroinflammation control.

“These results indicate that circulating [progranulin] levels might reflect the severity of neuronal loss and might be developed as a potential biomarker of [Parkinson’s disease],” the researchers wrote.

Progranulin deficiency has also been implicated in other neurodegenerative diseases besides Parkinson’s, including frontotemporal dementia, a group of dementias mainly affecting decision-making and behavior or language and speech, depending on the brain area that’s affected.

More research is necessary to investigate the protein’s diagnostic potential in Parkinson’s disease, the researchers advised.

A Phase 1 clinical trial in healthy volunteers (NCT04111666) is expected to test AL101, a therapeutic compound with a potential ability to raise progranulin levels in the brains of people with neurodegenerative diseases. But this study, listed as starting in December 2019, does not yet appear to be enrolling.