Rasagiline and rapid symptomatic motor effect in Parkinson's disease: review of literature.
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ABSTRACT:
SUBMITTER: Pistacchi M
PROVIDER: S-EPMC4381918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rasagiline (N-propargyl-1 (R)-aminoindan) is a novel propargylamine, irreversible, selective monoamine oxidase inhibitor for treatment of Parkinson's disease (PD), a progressive condition associated with degeneration of dopaminergic neurons in the substantia nigra. Rasagiline inhibits striatal dopamine metabolism, thereby providing relief from motor symptoms of PD. It may be dosed once daily and, unlike selegiline, it is metabolized to non-amphetamine compounds. In a large clinical trial, rasagiline has proved effective, safe, and well tolerated in early PD as monotherapy. In two phase III clinical trials in advanced PD with motor fluctuations, rasagiline as an adjunct to levodopa significantly decreases "off" time. In animal models of PD, data supports a neuroprotective effect of rasagiline, and its active metabolite aminoindan. Analysis of delayed-start clinical trial suggests the potential for disease modification, and further trials are examining this effect.
| S-EPMC2515917 | biostudies-literature
Project description:The use of adjunct rasagiline in levodopa-treated patients with Parkinson's disease and motor fluctuations is supported by findings from large-scale clinical studies. This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson's disease, as a product registration study.This 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson's disease and motor fluctuations. The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks. Secondary endpoints were Clinical Global Impressions - Improvement (CGI-I), and change in Unified Parkinson's Disease Rating Scale (UPDRS) Activities of daily living (ADL) and Motor scores. Patient well-being (EQ-5D), and the frequency of adverse events were also assessed.In total, 324 levodopa-treated patients were randomized to rasagiline 1 mg/day (n?=?165) or placebo (n?=?159). Over 16 weeks, rasagiline statistically significantly reduced the mean [95% confidence interval] total daily OFF time versus placebo (-?0.5 h [-?0.92, -?0.07]; p?=?0.023). There were also statistically significant improvements versus placebo in CGI-I (-?0.4 points [-?0.61, -?0.22]; p?<?0.001), UPDRS-ADL OFF (-?1.0 points [-?1.75, -?0.27]; p?=?0.008), and UPDRS-Motor ON (-?1.6 points [-?3.05, -?0.14]; p?=?0.032) scores, as well as the EQ-5D utility index (p?<?0.05). Rasagiline was safe and well tolerated.In levodopa-treated Chinese patients with Parkinson's disease and motor fluctuations, adjunct rasagiline 1 mg/day statistically significantly reduced OFF time, and improved daily function and overall well-being, versus placebo. Consistent with findings in other countries, adjunct rasagiline was proven efficacious and well tolerated in Chinese patients.NCT01479530. Registered 22 November 2011.
| S-EPMC6026338 | biostudies-literature
Project description:Background: Parkinson's disease (PD), a neurodegenerative disease characterised by bradykinesia, rest tremor and rigidit, affects approximately 6.1 million people worldwide. Although its aetiology was attributed to accumulation of misfolded alpha-synuclein species and subsequent loss of dopaminergic neurons in the substantia nigra, recently, systemic factors contributing to its initiation and progression have gained increasing recognition. Specifically, exosomes, a kind of extracellular vesicles in the size range of ∼30 to ∼200 nm, have been highlighted as crucial mediators in orchestrating the intricate intercellular communication in PD. Among its cargos, miRNAs, with its ability to promote target mRNA degradation and inihibit translation, have been identiifed as promising biomarkers and therpaeutic targets. Nonetheless, the effect of anti-parkinsonism medication on the serum exosome miRNA profiles of PD patients remain lagrely unexplored. Objective: To examine the effects of rasagiline, a potentially neuroprotective monoamine oxidase B inihibitor, on the serum exosome miRNA profile of PD patients.
2024-07-26 | GSE269776 | GEO
Project description:Background: Parkinson's disease (PD), a neurodegenerative disease characterised by bradykinesia, rest tremor and rigidit, affects approximately 6.1 million people worldwide. Although its aetiology was attributed to accumulation of misfolded alpha-synuclein species and subsequent loss of dopaminergic neurons in the substantia nigra, recently, systemic factors contributing to its initiation and progression have gained increasing recognition. Specifically, exosomes, a kind of extracellular vesicles in the size range of ∼30 to ∼200 nm, have been highlighted as crucial mediators in orchestrating the intricate intercellular communication in PD. Among its cargos, miRNAs, with its ability to promote target mRNA degradation and inihibit translation, have been identiifed as promising biomarkers and therpaeutic targets. Nonetheless, the effect of anti-parkinsonism medication on the serum exosome miRNA profiles of PD patients remain lagrely unexplored. Objective: To examine the effects of rasagiline, a potentially neuroprotective monoamine oxidase B inihibitor, on the serum exosome miRNA profile of PD patients.
2024-07-26 | GSE269775 | GEO
Project description:Background: Parkinson's disease (PD), a neurodegenerative disease characterised by bradykinesia, rest tremor and rigidit, affects approximately 6.1 million people worldwide. Although its aetiology was attributed to accumulation of misfolded alpha-synuclein species and subsequent loss of dopaminergic neurons in the substantia nigra, recently, systemic factors contributing to its initiation and progression have gained increasing recognition. Specifically, exosomes, a kind of extracellular vesicles in the size range of ∼30 to ∼200 nm, have been highlighted as crucial mediators in orchestrating the intricate intercellular communication in PD. Among its cargos, miRNAs, with its ability to promote target mRNA degradation and inihibit translation, have been identiifed as promising biomarkers and therpaeutic targets. Nonetheless, the effect of anti-parkinsonism medication on the serum exosome miRNA profiles of PD patients remain lagrely unexplored. Objective: To examine the effects of rasagiline, a potentially neuroprotective monoamine oxidase B inihibitor, on the serum exosome miRNA profile of PD patients.
2024-07-26 | GSE269779 | GEO
Project description:Background: Parkinson's disease (PD), a neurodegenerative disease characterised by bradykinesia, rest tremor and rigidit, affects approximately 6.1 million people worldwide. Although its aetiology was attributed to accumulation of misfolded alpha-synuclein species and subsequent loss of dopaminergic neurons in the substantia nigra, recently, systemic factors contributing to its initiation and progression have gained increasing recognition. Specifically, exosomes, a kind of extracellular vesicles in the size range of ∼30 to ∼200 nm, have been highlighted as crucial mediators in orchestrating the intricate intercellular communication in PD. Among its cargos, miRNAs, with its ability to promote target mRNA degradation and inihibit translation, have been identiifed as promising biomarkers and therpaeutic targets. Nonetheless, the effect of anti-parkinsonism medication on the serum exosome miRNA profiles of PD patients remain lagrely unexplored. Objective: To examine the effects of rasagiline, a potentially neuroprotective monoamine oxidase B inihibitor, on the serum exosome miRNA profile of PD patients.
2024-07-26 | GSE269777 | GEO
Project description:ObjectiveIdentifying neural activity biomarkers of brain disease is essential to provide objective estimates of disease burden, obtain reliable feedback regarding therapeutic efficacy, and potentially to serve as a source of control for closed-loop neuromodulation. In Parkinson's disease (PD), microelectrode recordings (MER) are routinely performed in the basal ganglia to guide electrode implantation for deep brain stimulation (DBS). While pathologically-excessive oscillatory activity has been observed and linked to PD motor dysfunction broadly, the extent to which these signals provide quantitative information about disease expression and fluctuations, particularly at short timescales, is unknown. Furthermore, the degree to which informative signal features are similar or different across patients has not been rigorously investigated. We sought to determine the extent to which motor error in PD across patients can be decoded on a rapid timescale using spectral features of neural activity.ApproachHere, we recorded neural activity from the subthalamic nucleus (STN) of subjects with PD undergoing awake DBS surgery while they performed an objective, continuous behavioral assessment that synthesized heterogenous PD motor manifestations to generate a scalar measure of motor dysfunction at short timescales. We then leveraged natural motor performance variations as a 'ground truth' to identify corresponding neurophysiological biomarkers.Main resultsSupport vector machines using multi-spectral decoding of neural signals from the STN succeeded in tracking the degree of motor impairment at short timescales (as short as one second). Spectral power across a wide range of frequencies, beyond the classic 'β' oscillations, contributed to this decoding, and multi-spectral models consistently outperformed those generated using more isolated frequency bands. While generalized decoding models derived across subjects were able to estimate motor impairment, patient-specific models typically performed better.SignificanceThese results demonstrate that quantitative information about short-timescale PD motor dysfunction is available in STN neural activity, distributed across various patient-specific spectral components, such that an individualized approach will be critical to fully harness this information for optimal disease tracking and closed-loop neuromodulation.
| S-EPMC8140652 | biostudies-literature
Project description:AimsTo investigate the effects of levodopa on the basal ganglia motor circuit (BGMC) in Parkinson's disease (PD).MethodsThirty PD patients with asymmetrical bradykinesia and 30 control subjects were scanned using resting-state functional MRI. Functional connectivity of the BGMC was measured and compared before and after levodopa administration in patients with PD. The correlation between improvements in bradykinesia and changes in BGMC connectivity was examined.ResultsIn the PD-off state (before medication), the posterior putamen and internal globus pallidus (GPi) had decreased connectivity while the subthalamic nucleus (STN) had enhanced connectivity within the BGMC relative to control subjects. Levodopa administration increased the connectivity of posterior putamen- and GPi-related networks but decreased the connectivity of STN-related networks. Improvements in bradykinesia were correlated with enhanced connectivity of the posterior putamen-cortical motor pathway and with decreased connectivity of the STN-thalamo-cortical motor pathway.ConclusionIn PD patients with asymmetrical bradykinesia, levodopa can partially normalize the connectivity of the BGMC with a larger effect on the more severely affected side. Moreover, the beneficial effect of levodopa on bradykinesia is associated with normalization of the striato-thalamo-cortical motor and STN-cortical motor pathways. Our findings inform the neural mechanism of levodopa treatment in PD.
| S-EPMC6492721 | biostudies-literature
Project description:The heterogeneity of Parkinson's disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundations of PD heterogeneity remain elusive. Genetic contributions to PD may be informative in understanding the underpinnings of PD subtypes. As such, recognizing genotype-phenotype associations may be crucial for successful gene therapy. We review the state of knowledge on the genetic architecture underlying PD subtypes, discussing the monogenic forms, as well as oligo- and polygenic risk factors associated with various PD subtypes. Based on our review, we argue for the unification of PD subtyping classifications, the dichotomy of studies on genetic factors and genetic modifiers of PD, and replication of results from previous studies.
| S-EPMC9632166 | biostudies-literature
Project description:Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however ?-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type ?-synuclein under the control of the mouse ?-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. ?-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.
| S-EPMC3616111 | biostudies-literature