David Devos

University of Lille Nord de France · Medical Pharmacology

Parkinson's disease (PD) is primarily characterized by three histological hallmarks: dopaminergic neuronal degeneration, α‐synuclein accumulation and iron deposition. Over the last years, neuroimaging, particularly magnetic resonance imaging (MRI) has provided invaluable insights into the mechanisms underlying the disease. However, no imaging metho...

Importance Interventions that substantially slow neurodegeneration are needed to address the growing burden of Alzheimer disease (AD) to societies worldwide. Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target. Objective To investigate whether the brain-permeable iron chelato...

Quantitative susceptibility mapping (QSM) and transcranial sonography (TCS) offer proximal evaluations of iron load in the substantia nigra. Our prospective study aimed to investigate the relationship between QSM and TCS measurements of nigral iron content in patients with Parkinson’s disease (PD). In secondary analyses, we wanted to explore the co...

Background The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects...

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, with a typical lifespan of 3-5 years. Altered metabolism is a key feature of ALS that strongly influences prognosis, with an increase in whole-body energy expenditure and changes in skeletal muscle metabolism, including greater reliance on fat o...

Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demo...

Continuous compensation of cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. However, dopamine does not cross the digestive and blood-brain barriers, and is rapidly oxidised. The new concept is continuous intra-cerebroventricular administration of anaerobic dopamine (A-dopamine) using a telemetry-controlled subcuta...

Background Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling. Objectives We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone‐ prolonged‐release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP....

Background Parkinson’s disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD,...

In 2011, the UK medical research charity Cure Parkinson’s set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson’s disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD...

Background: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease. Methods: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in perso...

Background and objectives The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs)...

Background NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson’s disease (PD). Methods Patients with PD were included in presurgical si...

An increasing number of studies indicate that ferroptosis, a lethal pathway initiated by excessive iron-dependent lipid peroxidation, and pivotal to the survival of dopaminergic neurons and the progression of Parkinson’s disease (PD), may be regulated by the lysosomal pathway. Mutation and loss of function of the lysosomal enzyme, glucocerebrosidas...

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a preferred treatment for parkinsonian patients with severe motor fluctuations. Proper targeting of the STN sensorimotor segment appears to be a crucial factor for success of the procedure. The recent introduction of directional leads theoretically increases stimulation spe...

Background: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. Methods: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo...

Parkinson’s disease (PD) is affecting about 1.2 million patients in Europe with a prevalence that is expected to have an exponential increment, in the next decades. This epidemiological evolution will be challenged by the low number of neurologists able to deliver expert care for PD. As PD is better recognized, there is an increasing demand from pa...

Background Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at...

Paracellular permeability across epithelial and endothelial cells is in large part regulated by apical intercellular junctions also referred to as the tight junctions (TJs). These junctions contribute to the spatial...

Postoperative apathy is a frequent symptom in Parkinson’s disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering and ii) direct effect of chronic stimula...

Background: Parkinson's disease (PD) affects all dimensions of the patient's and the caregiver's daily life. There are two questionnaires in German, Bela-A-k (for caregivers) and Bela-P-k (for PD patients), that can be used to assess the PD-related psychosocial burden in a dyad. The patient's and the caregiver's perspective of living with PD can b...

The dogma "One gene, one protein" is clearly obsolete since cells use alternative splicing and generate multiple transcripts which are translated into protein isoforms, but also use alternative translation initiation sites (TISs) and termination sites on a given transcript. Alternative open reading frames for individual transcripts give proteins or...

Iron accumulation has been associated with the etiology and progression of multiple neurodegenerative diseases (NDDs). The exact role of iron in these diseases is not fully understood, but an iron-dependent form of regulated cell death called ferroptosis could be key. Although there is substantial preclinical and clinical evidence that ferroptosis...

Background: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clini...

Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains as well as light chains. However, their edification is different from the ones found in B cells and they resemble aberrant immun...

Background: The monogenic forms of Parkinson's disease represent less than 10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. We aim to establish the interest of multiplex ligation-dependent probe amplification as a primary screening test and to propose clinical criteria...

BACKGROUND Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS...

The dogma “One gene, one protein” is clearly obsolete since cells use alternative splicing and generate multiple transcripts which are translated into protein isoforms, but also use alternative translation initiation sites and termination sites on a given transcripts. Alternative open reading frames for individual transcripts give proteins (the alt...

Background: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. Metho...

Ferroptosis, an iron-dependent regulated cell death triggered by high lipid peroxide levels, has been implicated in several neurodegenerative diseases, including Parkinson's disease (PD). Brain regions such as the striatum are highly rich in both peroxidation susceptible PUFAs and iron, which accumulate at a greater rate than age in PD. The exact m...

Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains as well as light chains. However, their edification is different from the ones found in B cells and resembles aberrant immunoglo...

Ferroptosis, first coined in 2012, is an iron-dependent regulated cell death (RCD) characterized by the accumulation of lipid peroxides to toxic levels. This mechanism is currently being evaluated as a target for a variety of diseases offering new opportunities for drug design and development. Recent reports uncovered acyl-CoA synthetase long-chain...

There is a continued unmet need for treatments that can slow Parkinson’s disease progression due to the lack of understanding behind the molecular mechanisms underlying neurodegeneration. Since its discovery, ferroptosis has been implicated in several diseases and represents a therapeutic target in Parkinson’s disease. Here, we use two highly relev...

Objectives To explore possible forms of domestic violence suffered by men with Parkinson’s disease (PD). Methods A qualitative study was conducted through face-to face interviews, followed by a conceptual content analysis. Forms of violence were predetermined as code categories according to a classification of mistreatment and a lack within Maslow...

Introduction There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulatio...

Background: Neuroferritinopathy is a rare inherited neurodegenerative disease with brain iron accumulation characterized by brain iron overload resulting in progressive movement disorders. No treatment is currently available. Objective: We assessed conservative iron chelation with deferiprone at 30 mg/kg/day on the disease progression with contr...

Objectives: We aimed to define brain iron distribution patterns in subtypes of early-onset Alzheimer's disease (EOAD) by the use of quantitative susceptibility mapping (QSM). Methods: EOAD patients prospectively underwent MRI on a 3-T scanner and concomitant clinical and neuropsychological evaluation, between 2016 and 2019. An age-matched contro...

Background Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson’s disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. Objecti...

Brain administration of human platelet lysates (HPL) is a potential emerging biotherapy of neurodegenerative and traumatic diseases of the central nervous system. HPLs being prepared from pooled platelet concentrates, thereby increasing viral risks, manufacturing processes should incorporate robust virus‐reduction treatments. We evaluated a 19 ± 2‐...

Spinal cord injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery below the injury site. Previously, we demonstrated that inflammation determines the fate of the physiopathology. To decipher the molecular mechanisms involved in this process, we performed a meta-a...

In this one‐year prospective study, Parkinson's disease (PD) patients with or without mania following STN‐DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postope...

Background An ongoing need during the COVID-19 pandemic has been the requirement for accurate and efficient point-of-care testing platforms to distinguish infected from non-infected people, and to differentiate SARS-CoV-2 infections from other viruses. Electrochemical platforms can detect the virus via its envelope spike protein by recording change...

Background Parkinson’s disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. Objective To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers asso...

Background Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in...

Background Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. Methods In a retrospective...

Introduction L’ajustement d’un traitement par apomorphine est complexe, consommateur en soins. L’actimétrie pourrait améliorer la prise en charge en limitant les déplacements des patients et en facilitant l’ajustement du traitement (télésurveillance). Objectifs Notre étude vise à évaluer l’impact de l’actimétrie en vie réelle, sur le traitement et...

Introduction Plusieurs études suggèrent des spécificités de personnalité dans la maladie de Parkinson (MP), principalement sur des populations de faible effectif et assez hétérogènes. Objectifs Décrire les dimensions de personnalité du Temperament and Character Inventory (TCI) sur une grande cohorte de patients parkinsoniens fluctuants et vérifier...

Background: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements...

Spinal Cord Injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery at the level of cavity. Previously, we demonstrated that inflammation determine the fate of the physiopathology. In an attempt to decipher the molecular mechanisms involved in this process, we perf...

Background Riluzole has been reported to be beneficial in patients with cerebellar ataxia; however, effectiveness in individual subtypes of disease is unclear due to heterogeneity in participants' causes and stages of disease. Our aim was to test riluzole in a single genetic disease, spinocerebellar ataxia type 2. Methods We did a randomised, doub...

Background Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson’s disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients’ quality of life (QoL) amelioration after D...

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant hereditary neurodegenerative disease caused by the expansion of a CAG-repeat in the ataxin-7 (ATXN7) gene, usually characterized by progressive cerebellar ataxia and retinal dystrophy. We report the case of a 45-year-old woman presenting with a rapid-onset amyotrophic lateral sclerosis (...

Abstract Background Interventional trials in amyotrophic lateral sclerosis (ALS) suffer from the heterogeneity of the disease as it considerably reduces statistical power. We asked if blood neurofilament light chains (NfL) could be used to anticipate disease progression and increase trial power. Methods In 125 patients with ALS from three independe...

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons leading to death within 3 years and without a curative treatment. Neurotrophic growth factors (NTFs) are pivotal for cell survival. A reason for the lack of patient efficacy with single recombinant NTF brain infusion is likely to be due to the synergisti...

Objective: To determine whether Parkinson's disease (PD) patients eligible to subthalamic deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) pre-operatively could be more at risk of poorer motor, non-motor and quality of life outcomes 12 months after surgery, compared to those without RBD. Methods: We analyzed the p...

Background In many clinical applications, evolution of a longitudinal marker is censored by an event occurrence, and, symmetrically, event occurrence can be influenced by the longitudinal marker evolution. In such frameworks joint modeling is of high interest. The Joint Latent Class Model (JLCM) allows to stratify the population into groups (classe...

Objective To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. Methods Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to...

Neuroinflammation, as defined by the presence of classically activated microglia, is thought to play a key role in numerous neurodegenerative disorders such as Alzheimer’s disease. While modulating neuroinflammation could prove beneficial against neurodegeneration, identifying its most relevant biological processes and pharmacological targets remai...

Traumatic brain injury leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from traumatic brain injury can be addressed not by a single therapeutic approach, but rather...

Parkinson's disease is a progressive neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. While mitigating neuroinflammation could prove beneficial for Parkinson's disea...

Introduction L’effet de la stimulation du noyau subthalamique (NST) sur les troubles du contrôle des impulsions (TCI) dans la maladie de Parkinson (MP) demeure controversé. Objectifs L’objectif était d’analyser l’évolution des TCI chez des patients parkinsoniens, entre l’état préopératoire et 1 an après stimulation du NST, et d’identifier des fact...