Phosphodiesterase 10A Decreases Alongside Dopamine in Parkinson Disease

Phosphodiesterase 10A levels, which are associated with motor symptom severity, plummet in middle-stage and advanced patients with Parkinson disease (PD), according to a new study.

The study included 78 subjects; of them, 17 had been recently diagnosed and were hardly presenting symptoms, 15 were in early levodopa treatment, 24 had moderate-advanced symptoms addressed with levodopa, and 22 were healthy controls.

All participants underwent phosphodiesterase 10A positron emission tomography, dopamine positron emission tomography, and a 3-Tesla MRI scan.

Gennaro Pagano, MD, MSc, led the team conducting the study—which was partially funded by the Michael J. Fox Foundation, among others. Investigators did not respond to requests for comment at the time of publication.

Early patients showed loss of phosphodiesterase in caudate and putamen (P< .001). Early levodopa-treated patients showed even greater loss in the caudate (P< .001; annual decline 3.6%) and putamen (P < .001; annual decline 2.8%), but also loss of dopamine in the putamen (P< .001; annual decline 6.8%).

The specific losses were also associated with one another. Lower phosphodiesterase correlated with lower dopamine in both the caudate (P< .001) and putamen (P< .01). As the disease’s duration increased, phosphodiesterase in the caudate (P< .001) and putamen (P< .01) decreased, as did dopamine in the putamen (P< .001).

Symptomatically, motor symptoms heightened alongside lowered phosphodiesterase in the caudate (P < .05) and putamen (P< .05), as well as lower dopamine in the putamen (P< .001).

Overall, the study showed that phosphodiesterase decreases alongside dopamine in PD, and the combination heightens motor symptoms of the disease as it progresses. This potentially opens a new avenue of research—akin to dopamine transporter imagining, but for phosphodiesterase instead&mdash;which would allow the disease’s progression to be tracked in greater detail.

In a video interview with MD Magazine®, Sarah Hamm-Alvarez, PhD, emphasized the importance of identifying early signals and/or biomarkers of Parkinson disease, such as the aforementioned loss of phosphodiesterase. The drugs currently used for treating PD are the same drugs used 40 years ago. When trying to develop new, alternative treatments, identifying earlier signs or biomarkers of PD becomes absolutely vital.

“Obviously, any diagnostic biomarker that could provide [diagnosis of] patients at an earlier state would be potentially of great benefit, whether it is a biomarker in bio fluid like tears or saliva or cerebrospinal fluid,” Hamm-Alvarez told MD Mag. “We're very excited about the potential for any biomarker to be able to be paired to new therapies.”

The study, “Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson’s disease,” was published online in the journal Movement Disorders.