Emmanuelle Pourcher

Laval University | ULAVAL · Faculty of Medicine

Background: Genetic, biologic and clinical data suggest that Parkinson’s disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access...

Background: Patients with Parkinson's disease chronically treated with levodopa commonly have delayed or unpredictable onset of its benefits after oral intake. In this study, we assessed the safety and efficacy of CVT-301, a self-administered levodopa oral inhalation powder, for the treatment of patients with Parkinson's disease during off periods...

Objectives: The objective of this study was to compare the efficacy and safety of oral and transdermal rivastigmine for postural instability in patients with Parkinson disease dementia (PDD) who were candidates for a cholinesterase inhibitor. The primary outcome was the change in mean velocity of the center of pressure (CoP) after 6 months. Second...

DNAJC13 mutations have been suggested to cause Parkinson’s disease (PD), yet subsequent studies reported conflicting results on this association. In the current study, we sequenced the coding region of DNAJC13 in a French-Canadian/French cohort of 528 PD patients and 692 controls. A total of 62 (11.7%) carriers of rare DNAJC13 variants were identif...

Background Treatment of motor fluctuations in Parkinson's disease (PD) remains an unmet challenge. Adenosine 2A (A2A) receptors are located along the indirect pathway and represent a potential target to enhance l-3,4-dihydroxyphenylalanine (l-DOPA) antiparkinsonian action.Methods This article summarizes the preclinical and clinical literature on A2...

In the management of Parkinson’s disease, chronic L-DOPA therapy is associated with the development of motor fluctuations and dyskinesias. Since L-DOPA is the most effective antiparkinsonian medication currently available, adjunctive medications that reduce or prevent fluctuations and dyskinesias could be of great value. Adenosine 2A (A2A) antagoni...

Background Two previous studies of SB742457, a 5-hydroxytryptamine (5-HT6) receptor antagonist, suggested the efficacy of improvements in cognition and global outcome in Alzheimer's disease (AD). Methods Two randomized, placebo-controlled trials investigated SB742457 15 and 35 mg daily in subjects with mild-to-moderate AD (Mini-Mental Health State...

Background: Many patients with Parkinson's disease have motor fluctuations despite treatment with available drugs. Tozadenant (SYN115) is an oral, selective adenosine A2A receptor antagonist that improves motor function in animal models of Parkinson's disease. We aimed to assess the safety and efficacy of tozadenant as an adjunct to levodopa in pa...

Importance Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.Objective To examine whether CoQ10 cou...

Objective IPX066 is an extended release carbidopa/levodopa formulation designed to rapidly attain and maintain therapeutic plasma concentrations for a prolonged duration, allowing dosing intervals of approximately 6 h. The objective was to assess the efficacy, safety, and impact on quality of life of IPX066 in the treatment of levodopa-naive Parkin...

This study investigated the long-term safety of rivastigmine (12 mg/d capsules, 9.5 mg/24 h patch) and effects on motor symptoms in patients with mild-to-moderately severe Parkinson disease dementia. This was a 76-week, prospective, open-label, randomized study in patients aged 50 to 85 years. Primary outcomes included incidence of, and discontinua...

Introduction The aim of this study was to assess the frequency of self-reported compulsive behaviours, depressive and stress symptoms and sleep disorders in a population of Restless legs patients treated with DA agonists. Reports by Tippmann-Peikert et al. (2007) and Ritz et al. (2006) extend the risk of developing DA agonists related impulse contr...

The subventricular zone retains its neurogenic capacity throughout life and, as such, is often considered a potential source for endogenous repair in neurodegenerative disorders. Because dopamine is believed to stimulate adult neurogenesis, we looked for possible variations in the dopaminergic innervation of the subventricular zone between cases of...

Recent studies suggest that walking on a treadmill improves gait, mobility, and quality of life of patients with Parkinson's disease (PD). Still, there is a need for larger-scale randomized controlled studies that demonstrate the advantages of treadmill training (TT) with control groups that receive similar amounts of attention. Moreover, to date,...

Large repeat expansions in the C9orf72 gene were recently reported to be a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Given some of the clinical and pathologic overlap between these 2 diseases and Parkinson's disease, we sought to evaluate the presence of these expansions in a cohort of French-Canadian patien...

Background: Preladenant is a selective adenosine A₂A receptor antagonist under investigation for Parkinson's disease treatment. Methods: A phase 2 36-week open-label follow-up of a double-blind study using preladenant 5 mg twice a day as a levodopa adjunct in 140 subjects with fluctuating Parkinson's disease was conducted. The primary end point...

Background: IPX066 is an oral, extended-release, capsule formulation of carbidopa-levodopa. We aimed to assess this extended-release formulation versus immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations. Methods: We did a phase 3, randomised, double-blind, double-dummy study at 68 academic and clinic...

Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Sca...

To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson's disease (PD) experiencing motor fluctuations. Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary effic...

Istradefylline (KW-6002) is a selective adenosine A(2A) receptor antagonist investigated as adjunctive therapy to levodopa in PD patients with motor response complications. In Phase 2b/3 studies, Istradefylline reduced OFF time without worsening troublesome dyskinesia and was well tolerated. A randomized, 12-week, double-blind, placebo-controlled p...

It has previously been shown that impairment of postural stability is a side effect of typical antipsychotic drugs, which are largely administered to control psychosis and behavioral symptoms in elderly patients. Surprisingly, no study has yet addressed this problem with second-generation antipsychotics. The objective of this study was to determine...

In contrast to our vast knowledge of the dopamine (DA) system, much less is known about the involvement of serotonin (5-HT) in neurodegenerative diseases affecting the basal ganglia. Therefore, we designed a study that aimed at characterizing the status of the striatal DA and 5-HT systems in patients who suffered from either Parkinson's (PD) or Hun...

Postural instability is a concern in several neurologic conditions and also among the elderly. Dysfunction in serotonergic, noradrenergic, and dopaminergic pathways may be involved in the etiology of postural imbalance. The objective of this case report was to quantify, using computerized posturography, substitution with venlafaxine, and later levo...

Preladenant is an adenosine A2A receptor antagonist. In animal models of Parkinson's disease, preladenant monotherapy improves motor function without causing dyskinesia and, as an adjunct to levodopa, it improves motor function without worsening dyskinesia. We aimed to assess the efficacy and safety of preladenant in patients with Parkinson's disea...

Dopamine exerts a robust promoting effect on adult neurogenesis. Here, we report the presence of an intense dopamine (tyrosine hydroxylase immunoreactive) zone along the ventricular border of the caudate nucleus in patients with Huntington's disease, but not in age-matched controls. This thin (150-400 microm) paraventricular zone was composed of nu...

The neuropsychological literature on the processing of emotions in Parkinson's disease (PD) reveals conflicting evidence about the role of the basal ganglia in the recognition of facial emotions. Hence, the present study had two objectives. One was to determine the extent to which the visual processing of emotions and objects differs in PD. The oth...

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was c...

Previous studies had revealed no specific effect under haloperidol (typical) and risperidone (atypical) neuroleptic (NLP) treatments for schizophrenia (SZ) on a variety of neurocognitive functions relying on the dopaminergic meso-cortico-limbic system (Rémillard et al., 2005, 2008). Considering the different affinities of D2 dopamine receptors for...

A therapy that slows disease progression is the major unmet need in Parkinson's disease. In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2...

Depression in Idiopathic Parkinson's disease (IPD) is frequent, difficult to recognize, under managed and has a profound impact on quality of life. Current categorization of diagnosis in psychiatry poorly applies to the protean manifestations of mood disorders presented by parkinsonian patients. In this study we have chosen to dissect the state of...

Speech is the sound wave produced by the vibration of the vocal chords finely tuned by the supraglottal articulators: the tongue, the lips, and the jaw modulate the vocal tract shape to produce sounds that are distinctive enough to be distinguished. But how can people who suffer from a motor control disease such as Parkinson's disease (PD) produce...

Parkinson disease (PD) is a neurodegenerative disorder characterized by bradykinesia and at least one of the following primary features: truncal and limb muscle rigidity, resting tremor, and postural instability. Protein aggregates known as Lewy bodies found in dopaminergic neurons of the substantia nigra are deemed to be the major pathological hal...

Huntington's disease (HD) is characterized by the atrophy of the striatum due to losses of projection neurons, while interneurons are relatively spared. However, little is known about the fate of the large interneurons that express calretinin (Cr) in HD. We addressed this issue by applying a double immunofluorescent labeling technique to postmortem...

There is evidence in the literature that cognitive functions in schizophrenia (SC) may be improved by atypical neuroleptics (NLPs) in contrast to typical medication, but there is still controversy regarding this apparent superiority of atypical drugs. In this study, we assessed the differential effects of risperidone and haloperidol on verbal memor...

An old founder mutation (G2019S) was found with high frequency in the North African Arabs (30%) and Ashkenazi Jews (18% ). Objective: Demonstrate if mutations in the LRRK2 gene are a significant cause of Parkinson's disease (PD) in the French-Canadian founder population. Cases were recruited through a designated movement disorder clinic in Quebec C...

Idiopathic Parkinson's disease (IPD) patients and matched healthy participants were compared on a non-motor procedural task involving semantically related inverted word pairs, and 3 months later to determine the extent of skill consolidation. IPD patients were found to acquire new procedural skills necessary to read these inverted words, thus indic...

Objective: To compare the efficacy, safety and tolerability of sumanirole with placebo in patients with idiopathic restless legs syndrome (RLS). Methods: In this double-blind, placebo-controlled, randomized, parallel-group, dose–response study, 270 patients with idiopathic RLS were enrolled and randomized to receive sumanirole 0.5, 1.0, 2.0, or 4.0...

In patients with dementia associated with Parkin-son's disease (PD), the efficacy and safety of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, were previously demonstrated in a 24-week double-blind placebo controlled trial. Our objective was to determine whether benefits were sustained over the long term. Following th...

The aims of this study were to assess the safety, tolerability, and efficacy of sumanirole, a highly selective D 2 dopamine receptor agonist, versus placebo in subjects with advanced Parkinson's disease (PD), and to demonstrate nonin-feriority of sumanirole to ropinirole. In this flexible-dose, ran-domized, double-blind, double-dummy, parallel-grou...

Cognitive dysfunctions (as in memory, attention and executive function) have been recognized as fundamental features of schizophrenia. Executive dysfunction is a major obstacle to functional outcome, community functioning and rehabilitation success and it is crucial to assess the effects of so-called neuroleptic (NLP) medications in this domain of...