Dopamine D1 Agonists May Benefit Patients With Late-Stage Parkinson's

The study covered in this summary was published on MedRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

• D1/5 agonists may offer potential benefit for patients with late-stage Parkinson's disease (LsPD). 

• Caregiver perspectives with mixed method analyses may overcome limitations in standard rater/clinician-based evaluations. 

• Further studies are warranted and need to integrate caregiver input as an essential component of outcome evaluations.

Why This Matters

• Patients with LsPD experience many nonmotor symptoms, including anxiety/depression, pain, sleep disorders, cognitive decline, apathy, and social withdrawal, some of which predate motor dysfunction.

• As PD patients advance to LsPD, there is a high burden for family and caregivers, and higher healthcare costs compared with early and mid-stage patients.

• Current pharmacotherapy has limited efficacy and intolerable side effects in LsPD patients whose daily life depends primarily on caregivers and palliative care.

• Because postsynaptic cytoarchitecture in patients with LsPD is largely preserved despite dopamine neuron degeneration, targeting one or more of the postsynaptic dopamine receptor populations could offer marked therapeutic benefit.

Study Design

• A double-blind controlled phase 1a/1b study compared the D1/5 agonist PF-06412562 to levodopa/carbidopa in six patients with LsPD. 

• Assessments included standard quantitative scales of motor function, alertness, and cognition at baseline and thrice daily during drug testing. 

• Clinicians and caregivers completed clinical impression of change questionnaires and caregivers participated in a qualitative exit interview. 

• Blinded triangulation of quantitative and qualitative data was used to integrate findings.

Key Results

• Neither traditional scales, nor clinician impression of change, detected consistent differences between treatments in the five participants who completed the study. 

• The overall caregiver data strongly favored PF-06412562 over levodopa in 4 of 5 patients. 

• The most meaningful improvements converged on motor, alertness, and engagement.

Limitations

• With no prior experience available for interventional studies in LsPD, the design had to focus on the safety and feasibility, thus limiting both the number of subjects and permitted treatment duration (2 days).

• Efficacy was a second primary endpoint, but it could be evaluated only if the theoretical safety concerns had not terminated the study.

Disclosures

• This study was funded in part by Pfizer, Inc and the drug was also supplied by Pfizer. The study was also supported by the Penn State College of Medicine Translational Brain Research Center. All analyses, interpretations, and conclusions are those of the authors and not the research sponsors. 

• The study was reviewed and approved by the Penn State Health Institutional Review Board.

This is a summary of a preprint research study, "Dopamine D1 agonist effects in late-stage Parkinson's disease," written by Mechelle M. Lewis from the Departments of Neurology, Penn State Milton S. Hershey Medical Center and Penn State College of Medicine, and colleagues on MedRxiv.org, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

For more news, follow Medscape on Facebook, Twitter, Instagram, YouTube, and LinkedIn

© 2022  WebMD, LLC

Send news tips to news@medscape.net.

Cite this: Dopamine D1 Agonists May Benefit Patients With Late-Stage Parkinson's - Medscape - May 18, 2022.