The Added Benefit of Opicapone When Used Early in Parkinson's Disease Patients With Levodopa-Induced Motor Fluctuations: A Post-hoc Analysis of BIPARK-I and -II

Introduction: Opicapone (OPC) was efficacious in reducing OFF-time in two pivotal trials in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (BIPARK-I and -II). Post-hoc analyses of these trials evaluated the efficacy of OPC following pre-defined segmentation of the wide spectrum of motor fluctuations in PD.Methods: Data from matching treatment arms in BIPARK-I and -II were combined for the placebo (PLC) and OPC 50-mg groups, and exploratory post-hoc analyses were performed to investigate the efficacy of OPC 50 mg vs. PLC in subgroups of patients who were in “earlier” vs. “later” stages of both their disease course (e.g., duration of PD <6 years vs. ≥6 years) and levodopa treatment pathway (e.g., number of daily levodopa intakes <4 vs. ≥4). Efficacy variables included changes from baseline in absolute OFF-time and total ON-time.Results: The Full Analysis Set included 517 patients (PLC, n = 255; OPC 50 mg, n = 262). OPC 50 mg was significantly more effective than PLC in reducing OFF-time and increasing ON-time in the majority of subgroup analyses (p < 0.05). Moreover, patients in “earlier” stages of both their disease course and levodopa treatment pathway experienced numerically greater efficacy when using OPC 50 mg, in comparison with those in “later” stages.Conclusion: OPC 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in PD patients. There was also a signal for enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway.

Case Report: Levodopa - induced creative awakening in a patient with Parkinson’s disease

Parkinson’s disease is primarily a neurodegenerative disorder and presents with neurological symptoms but it can also have accompanying psychiatric symptoms. In addition, in some patients with Parkinson’s disease there can be an awakening of their creativity, which can take several forms. Such creativity can be seen in art-naïve patients or in whom the creativity lay dormant. Although the precise mechanism for this phenomenon is not understood, treatment with levodopa and dopamine agonists have been considered responsible in some cases. Here, we describe a patient with Parkinson’s disease in whom levodopa treatment triggered a latent creative skill that was dormant since childhood. Through the patient’s own and his wife’s eyes, we discuss the clinical benefits of this phenomenon.

Riluzole Administration to Rats with Levodopa-Induced Dyskinesia Leads to Loss of DNA Methylation in Neuronal Genes

Dyskinesias are characterized by abnormal repetitive involuntary movements due to dysfunctional neuronal activity. Although levodopa-induced dyskinesia, characterized by tic-like abnormal involuntary movements, has no clinical treatment for Parkinson’s disease patients, animal studies indicate that Riluzole, which interferes with glutamatergic neurotransmission, can improve the phenotype. The rat model of Levodopa-Induced Dyskinesia is a unilateral lesion with 6-hydroxydopamine in the medial forebrain bundle, followed by the repeated administration of levodopa. The molecular pathomechanism of Levodopa-Induced Dyskinesia is still not deciphered; however, the implication of epigenetic mechanisms was suggested. In this study, we investigated the striatum for DNA methylation alterations under chronic levodopa treatment with or without co-treatment with Riluzole. Our data show that the lesioned and contralateral striata have nearly identical DNA methylation profiles. Chronic levodopa and levodopa + Riluzole treatments led to DNA methylation loss, particularly outside of promoters, in gene bodies and CpG poor regions. We observed that several genes involved in the Levodopa-Induced Dyskinesia underwent methylation changes. Furthermore, the Riluzole co-treatment, which improved the phenotype, pinpointed specific methylation targets, with a more than 20% methylation difference relative to levodopa treatment alone. These findings indicate potential new druggable targets for Levodopa-Induced Dyskinesia.

Effects of Helicobacter pylori on Levodopa Pharmacokinetics

Background: Infection with Helicobacter pylori seems overrepresented in Parkinson’s disease. Clinical observations suggest a suboptimal treatment effect of levodopa in Helicobacter positive patients. Objective: Describe and explain the connection between a Helicobacter pylori infection of the upper gut and changes in pharmacokinetics of oral levodopa treatment in Parkinson’s disease. Methods: PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: Bioavailability, drug metabolism, dyskinesia, Helicobacter, L-dopa, levodopa, motor control, pharmacodynamics, pharmacokinetics, prevalence, unified Parkinson’s disease rating scale. Results: The prevalence of Helicobacter pylori in Parkinson’s disease patients is reported to be about 1.6-fold higher than in a control population in some studies. Helicobacter has therefore been assumed to be linked to Parkinson’s disease, but the mechanism is unclear. As regards symptoms and treatment, patients with Parkinson’s disease on levodopa therapy and with Helicobacter pylori infection display worse motor control than those without Helicobacter infection. Eradication of the infection improves levodopa response in Parkinson’s disease, likely as a consequence of an increased oral pre-systemic bioavailability of levodopa, likely to be explained by reduced Helicobacter-dependent levodopa consumption in the stomach. In addition, small intestinal bacterial overgrowth may also have an impact on the therapeutic setting for levodopa treatment but is less well established. Conclusion: Eradication of Helicobacter pylori improves levodopa bioavailability resulting in improved motor control. Eradication of Helicobacter should be considered in patients with poor symptomatic control and considerable motor fluctuations.