Academic Journal

Dopamine D1 Agonists: First Potential Treatment for Late-Stage Parkinson’s Disease

التفاصيل البيبلوغرافية
العنوان: Dopamine D1 Agonists: First Potential Treatment for Late-Stage Parkinson’s Disease
المؤلفون: Mechelle M. Lewis, Lauren J. Van Scoy, Sol De Jesus, Jonathan G. Hakun, Paul J. Eslinger, Julio Fernandez-Mendoza, Lan Kong, Yang Yang, Bethany L. Snyder, Natalia Loktionova, Sridhar Duvvuri, David L. Gray, Xuemei Huang, Richard B. Mailman
المصدر: Biomolecules, Vol 13, Iss 5, p 829 (2023)
بيانات النشر: MDPI AG, 2023.
سنة النشر: 2023
المجموعة: LCC:Microbiology
مصطلحات موضوعية: dopamine D1 agonists, late-stage Parkinson’s disease, dopamine D1 receptors, clinical trial, Microbiology, QR1-502
الوصف: Current pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinson’s disease (LsPD) patients whose daily life depends primarily on caregivers and palliative care. Clinical metrics inadequately gauge efficacy in LsPD patients. We explored if a D1/5 dopamine agonist would have efficacy in LsPD using a double-blind placebo-controlled crossover phase Ia/b study comparing the D1/5 agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. Caregiver assessment was the primary efficacy measure because caregivers were with patients throughout the study, and standard clinical metrics inadequately gauge efficacy in LsPD. Assessments included standard quantitative scales of motor function (MDS-UPDRS-III), alertness (Glasgow Coma and Stanford Sleepiness Scales), and cognition (Severe Impairment and Frontal Assessment Batteries) at baseline (Day 1) and thrice daily during drug testing (Days 2–3). Clinicians and caregivers completed the 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. Neither traditional scales nor clinician impression of change detected consistent differences between treatments in the five participants who completed the study. Conversely, the overall caregiver data strongly favored PF-06412562 over levodopa in four of five patients. The most meaningful improvements converged on motor, alertness, and functional engagement. These data suggest for the first time that there can be useful pharmacological intervention in LsPD patients using D1/5 agonists and also that caregiver perspectives with mixed method analyses may overcome limitations using methods common in early-stage patients. The results encourage future clinical studies and understanding of the most efficacious signaling properties of a D1 agonist for this population.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2218-273X
Relation: https://www.mdpi.com/2218-273X/13/5/829; https://doaj.org/toc/2218-273X
DOI: 10.3390/biom13050829
URL الوصول: https://doaj.org/article/7cc757351af94200a6c84001e84bd141
رقم الانضمام: edsdoj.7cc757351af94200a6c84001e84bd141
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2218273X
DOI:10.3390/biom13050829