Dataset Information

Movement Disorders in Prionopathies: A Systematic Review.

ABSTRACT: Background:Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described. Methods:We performed a systematic review of case reports and case series of pathologically- and genetically confirmed prionopathies. Timing of symptom and movement disorder onset were documented. Continuous variables were compared between two groups using the Wilcoxon rank sum test and between multiple groups using Kruskal-Wallis test. Categorical variables were compared using Fisher's exact test. Results:A total of 324 cases were included in this analysis. Movement disorders were a common feature at the onset of symptoms in most prionopathies. Gait ataxia was present in more than half of cases in all types of prionopathies. The prevalence of limb ataxia (20%) and myoclonus (24%) was lower in Gerstmann-Sträussler-Scheinker disease compared to other prionopathies (p ? 0.004). Myoclonus was common but often a later feature in sporadic Creutzfeldt-Jakob disease (2 months before death). Chorea was uncommon but disproportionately prevalent in variant Creutzfeldt-Jakob disease (30% of cases; p < 0.001). In genetic Creutzfeldt-Jakob disease, E200K PRNP carriers exhibited gait and limb ataxia more often when compared to other mutation carriers. Discussion:Movement disorders are differentially present in the course of the various prionopathies. The movement phenomenology and appearance are associated with the type of prion disease and the PRNP genotype and likely reflect the underlying pattern of neurodegeneration. Reliance on myoclonus as a diagnostic feature of sporadic Creutzfeldt-Jakob disease may delay its recognition given its relatively late appearance in the disease course.

SUBMITTER: Rodriguez-Porcel F

PROVIDER: S-EPMC6925394 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Movement Disorders in Prionopathies: A Systematic Review.

Rodriguez-Porcel Federico F Ciarlariello Vinícius Boaratti VB Dwivedi Alok K AK Lovera Lilia L Da Prat Gustavo G Lopez-Castellanos Ricardo R Suri Ritika R Laub Holly H Walker Ruth H RH Barsottini Orlando O Pedroso José Luiz JL Espay Alberto J AJ

Tremor and other hyperkinetic movements (New York, N.Y.) 20191212

<h4>Background</h4>Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described.<h4>Methods</h4>We performed a systematic review of case reports and case series of pathologically- and genetically confirmed prionopathies. Timing of symptom and movement disorder onset were documented. Continuous variables were compared between two groups using the Wilcoxon rank sum test and between multiple groups using Kruskal-Wallis test. Categorical vari ...[more]

PMID: 31871824

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Project description:Introduction: We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to modulate the expression of one or more genes to achieve a therapeutic benefit. Methods: We systematically reviewed movement disorders gene therapy clinical trials from PubMed and ClinicalTrials.gov using a searching strategy that included Parkinson disease (PD), Huntington disease (HD), amino acid decarboxylase (AADC) deficiency, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dystonia, tremor, ataxia, and other movement disorders. Data extracted included study characteristics, investigational product, route of administration, safety/tolerability, motor endpoints, and secondary outcomes (i.e., neuroimaging, biomarkers). Results: We identified a total of 46 studies focusing on PD (21 published and nine ongoing), HD (2 published and 5 ongoing), AADC deficiency (4 published and 2 ongoing), MSA (2 ongoing), and PSP (1 ongoing). In PD, intraparenchymal infusion of viral vector-mediated gene therapies demonstrated to be safe and showed promising preliminary data in trials aiming at restoring the synthesis of dopamine, enhancing the production of neurotrophic factors, or modifying the functional interaction between different nodes of the basal ganglia. In HD, monthly intrathecal delivery of an antisense oligonucleotide (ASO) targeting the huntingtin protein (HTT) mRNA proved to be safe and tolerable, and demonstrated a dose-dependent reduction of the cerebrospinal fluid levels of mutated HTT, while a small phase-I study testing implantable capsules of cells engineered to synthesize ciliary neurotrophic factor failed to show consistent drug delivery. In AADC deficiency, gene replacement studies demonstrated to be relatively safe in restoring catecholamine and serotonin synthesis, with promising outcomes. Ongoing movement disorders clinical trials are focusing on a variety of gene therapy approaches including alternative viral vector serotypes, novel recombinant genes, novel delivery techniques, and ASOs for the treatment of HD, MSA, and distinct subtypes of PD (LRRK2 mutation or GBA1 mutation carriers). Conclusion: Initial phase-I and -II studies tested the safety and feasibility of gene therapy in PD, HD, and AADC deficiency. The ongoing generation of clinical trials aims to test the efficacy of these approaches and explore additional applications for gene therapy in movement disorders.

Dataset Information

Movement Disorders in Prionopathies: A Systematic Review.

Publications

Movement Disorders in Prionopathies: A Systematic Review.

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