ORCID Profile
0000-0003-2610-1291
Current Organisations
Beaumont Hospital
,
Health Service Executive
,
Trinity College Dublin
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Publisher: Springer Science and Business Media LLC
Date: 25-07-2016
DOI: 10.1038/NG.3626
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-09-2018
DOI: 10.1212/WNL.0000000000006317
Abstract: To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King's clinical disease stage at time of testing. Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King's stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores. ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems.
Publisher: JMIR Publications Inc.
Date: 22-09-2021
DOI: 10.2196/28766
Abstract: Despite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients’ ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters mediate the development of benefit-to-burden criteria for innovative technology and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. We define two key end products of the road map: (1) a set of reliable digital parameters to capture data collected under free-living conditions that reflect patient-centric measures and facilitate clinical decision making and (2) an integrated, open-source system that provides personalized feedback to patients, health care providers, clinical researchers, and caregivers and is linked to a flexible and adaptable platform that integrates patient data in real time. Given the ever-changing care needs of patients and the relentless progression rate of motor neuron disease, the adoption of digital health care technology will significantly benefit the delivery of care and accelerate the development of effective treatments.
Publisher: BMJ
Date: 11-03-2017
Abstract: Prospective population based-registers of amyotrophic lateral sclerosis (ALS) have operated in Europe for over two decades, and have provided important insights into our understanding of ALS. Here, we review the benefits that population registers have brought to the understanding of the incidence, prevalence, phenotype and genetics of ALS and outline the core operating principles that underlie these registers and facilitate international collaboration. Going forward, we offer lessons learned from our collective experience of operating population-based ALS registers in Europe for over two decades, focusing on register design, maintenance, identification and management of bias and the value of cross-national harmonisation and integration.
Publisher: Elsevier BV
Date: 03-2018
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-02-2022
DOI: 10.1126/SCITRANSLMED.ABJ0264
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 s les passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Publisher: Elsevier BV
Date: 11-2013
Publisher: Springer Science and Business Media LLC
Date: 28-03-2017
DOI: 10.1038/TP.2016.292
Abstract: Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33 female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497 log 10 Bayes Factor=8.08) but failed to replicate in an independent European s le ( P =0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
Publisher: BMJ
Date: 23-09-2016
Abstract: The 457 (8.95%) of 4925 ALS cases carried the This study represents the largest combined analysis of the prognostic characteristics of the
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-05-2017
DOI: 10.1212/WNL.0000000000004038
Abstract: Population-based disease registers identify and characterize all cases of disease, including those that might otherwise be neglected. Prospective population-based registers in neurodegeneration are necessary to provide comprehensive data on the whole phenotypic spectrum and can guide planning of health services. With the exception of the rare disease amyotrophic lateral sclerosis, few complete population-based registers exist for neurodegenerative conditions. Incomplete ascertainment, limitations and uncertainty in diagnostic categorization, and failure to recognize sources of bias reduce the accuracy and usefulness of many registers. Common biases include population stratification, the use of prevalent rather than incident cases in earlier years, changes in disease understanding and diagnostic criteria, and changing demographics over time. Future registers are at risk of funding shortfalls and changes to privacy legislation. Notwithstanding, as heterogeneities of clinical phenotype and disease pathogenesis are increasingly recognized in the neurodegenerations, well-designed longitudinal population-based disease registers will be an essential requirement to complete clinical understanding of neurodegenerative diseases.
Publisher: Oxford University Press (OUP)
Date: 13-11-2013
DOI: 10.1093/HMG/DDT574
Abstract: Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within in iduals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control in iduals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Public Library of Science (PLoS)
Date: 11-04-2012
Publisher: JMIR Publications Inc.
Date: 14-03-2021
Abstract: espite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients’ ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters mediate the development of benefit-to-burden criteria for innovative technology and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. We define two key end products of the road map: (1) a set of reliable digital parameters to capture data collected under free-living conditions that reflect patient-centric measures and facilitate clinical decision making and (2) an integrated, open-source system that provides personalized feedback to patients, health care providers, clinical researchers, and caregivers and is linked to a flexible and adaptable platform that integrates patient data in real time. Given the ever-changing care needs of patients and the relentless progression rate of motor neuron disease, the adoption of digital health care technology will significantly benefit the delivery of care and accelerate the development of effective treatments.
Publisher: Elsevier BV
Date: 10-2010
Publisher: Springer Science and Business Media LLC
Date: 15-04-2016
DOI: 10.1038/NCOMMS11253
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified a CCNF missense mutation at this locus. Interrogation of international cohorts identified additional novel CCNF variants in familial and sporadic ALS and FTD. Enrichment of rare protein-altering CCNF variants was evident in a large sporadic ALS replication cohort. CCNF encodes cyclin F, a component of an E3 ubiquitin–protein ligase complex (SCF Cyclin F ). Expression of mutant CCNF in neuronal cells caused abnormal ubiquitination and accumulation of ubiquitinated proteins, including TDP-43 and a SCF Cyclin F substrate. This implicates common mechanisms, linked to protein homeostasis, underlying neuronal degeneration.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.NEUROBIOLAGING.2012.07.020
Abstract: The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival.
Publisher: Wiley
Date: 27-06-2014
DOI: 10.1002/ANA.24198
Publisher: BMJ
Date: 08-03-2019
Abstract: To investigate whether exposure to particulates and combustion products may explain the association between certain occupations and amyotrophic lateral sclerosis (ALS) risk in a large, multicentre, population-based, case–control study, based on full job histories, using job-exposure matrices, with detailed information on possible confounders. Population-based patients with ALS and controls were recruited from five registries in the Netherlands, Ireland and Italy. Demographics and data regarding educational level, smoking, alcohol habits and lifetime occupational history were obtained using a validated questionnaire. Using job-exposure matrices, we assessed occupational exposure to silica, asbestos, organic dust, contact with animals or fresh animal products, endotoxins, polycyclic aromatic hydrocarbons and diesel motor exhaust. Multivariate logistic regression models adjusting for confounding factors were used to determine the association between these exposures and ALS risk. We included 1557 patients and 2922 controls. Associations were positive for all seven occupational exposures (ORs ranging from 1.13 to 1.73 for high vs never exposed), and significant on the continuous scale for silica, organic dust and diesel motor exhaust (p values for trend ≤0.03). Additional analyses, adding an exposure (one at a time) to the model in the single exposure analysis, revealed a stable OR for silica. We found similar results when patients with a C9orf72 mutation were excluded. In a large, multicentre study, using harmonised methodology to objectively quantify occupational exposure to particulates and combustion products, we found an association between ALS risk and exposure to silica, independent of the other occupational exposures studied.
Publisher: Frontiers Media SA
Date: 09-11-2017
Publisher: BMJ
Date: 22-06-2017
Publisher: Elsevier BV
Date: 10-2016
Publisher: Cold Spring Harbor Laboratory
Date: 08-09-2017
Abstract: Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded s les as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type s les were correctly classified as wild type by this method with the remaining three s les identified as possible expansions. We further applied our algorithm to a set of 152 s les in which every s le had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-05-2017
DOI: 10.1126/SCITRANSLMED.AAD9157
Abstract: Annexin A11 mutations, implicated in ALS, prevent binding to calcyclin and induce the formation of cytoplasmic inclusions.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2019
DOI: 10.1038/S41598-019-42091-3
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 in iduals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. In this largest exome-wide study of rare variants in ALS to date, we performed single-variant association testing, gene-based burden, and exome-wide in idual set-unique burden (ISUB) testing to identify single or aggregated rare variation that modifies disease risk. In single-variant testing no variants reached exome-wide significance, likely due to limited statistical power. Gene-based burden testing of rare non-synonymous and loss-of-function variants showed NEK1 as the top associated gene. ISUB analysis did not show an increased exome-wide burden of deleterious variants in patients, possibly suggesting a more region-specific role for rare variation. Complete summary statistics are released publicly. This study did not implicate new risk loci, emphasizing the immediate need for future large-scale collaborations in ALS that will expand available s le sizes, increase genome coverage, and improve our ability to detect rare variants associated to ALS.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2009
DOI: 10.1038/NG.442
Abstract: We conducted a genome-wide association study among 2,323 in iduals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected in iduals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
Publisher: American Medical Association (AMA)
Date: 07-2016
Publisher: Elsevier BV
Date: 03-2018
Publisher: BMJ
Date: 21-08-2019
Abstract: We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case–control studies and explored the independent effects of intensity, duration and time-since-quitting. ALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (*Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models. Analyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk OR=1.26 (95% CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (p trend =0.001) rather than intensity (p trend =0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (p trend .0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration. Our findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger.
Publisher: Springer Science and Business Media LLC
Date: 28-06-2018
Publisher: Oxford University Press (OUP)
Date: 10-01-2019
DOI: 10.1093/AJE/KWY287
Abstract: We explored the associations of occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and electric shocks with the risk of amyotrophic lateral sclerosis (ALS) in a pooled case-control study (European Multidisciplinary ALS Network Identification to Cure Motor Neurone Degeneration (Euro-MOTOR)) of data from 3 European countries. ALS patients and population-based controls were recruited in Ireland, Italy, and the Netherlands between 2010 and 2015. Lifetime occupational and lifestyle histories were obtained using structured questionnaires. We applied previously developed job exposure matrices assigning exposure levels to ELF-MF and potential for electric shocks. Odds ratios and 95% confidence intervals were estimated by means of logistic regression for exposure to either ELF-MF or electric shocks, adjusted for age, sex, study center, education, smoking, and alcohol consumption and for the respective other exposure. Complete occupational histories and information on confounding variables were available for 1,323 clinically confirmed ALS cases and 2,704 controls. Both ever having had exposure to ELF-MF above the background level (odds ratio = 1.16, 95% confidence interval: 1.01, 1.33) and ever having had potential exposure above background for electric shocks (odds ratio = 1.23, 95% confidence interval: 1.05, 1.43) were associated with ALS. Adjustment for the respective other exposure resulted in similar risk estimates. Heterogeneity in risks across study centers was significant for both exposures. Our findings support possible independent associations of occupational exposure to ELF-MF and electric shocks with the risk of ALS.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Wiley
Date: 15-01-2021
DOI: 10.1002/ANA.26009
Publisher: Springer Science and Business Media LLC
Date: 21-03-2017
DOI: 10.1038/NCOMMS14774
Abstract: We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique in iduals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6 P =1 × 10 −4 ) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS ( P =8.4 × 10 −7 ). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08–1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.
Publisher: BMJ
Date: 13-02-2019
Abstract: Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer’s disease (AD), Lewy body dementia (LBD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are associated with changes in brain networks. However, the underlying neurophysiological pathways driving pathological processes are poorly defined. The gap between what imaging can discern and underlying pathophysiology can now be addressed by advanced techniques that explore the cortical neural synchronisation, excitability and functional connectivity that underpin cognitive, motor, sensory and other functions. Transcranial magnetic stimulation can show changes in focal excitability in cortical and transcortical motor circuits, while electroencephalography and magnetoencephalography can now record cortical neural synchronisation and connectivity with good temporal and spatial resolution. Here we reflect on the most promising new approaches to measuring network disruption in AD, LBD, PD, FTD, MS, and ALS. We consider the most groundbreaking and clinically promising studies in this field. We outline the limitations of these techniques and how they can be tackled and discuss how these novel approaches can assist in clinical trials by predicting and monitoring progression of neurophysiological changes underpinning clinical symptomatology.
Publisher: Oxford University Press (OUP)
Date: 20-11-2013
DOI: 10.1093/HMG/DDT587
Publisher: Proceedings of the National Academy of Sciences
Date: 02-06-2009
Abstract: Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U.S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent s le set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genome-wide significant result ( P = 1.84 × 10 −8 ) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability.
Publisher: Elsevier BV
Date: 03-2011
Publisher: Elsevier BV
Date: 11-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2009
Publisher: Informa UK Limited
Date: 13-12-2017
Publisher: Springer Science and Business Media LLC
Date: 25-07-2016
DOI: 10.1038/NG.3622
Publisher: Springer Science and Business Media LLC
Date: 11-10-2011
DOI: 10.1038/NRNEUROL.2011.153
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results in progressive loss of bulbar and limb function. Patients typically die from respiratory failure within 3 years of symptom onset. The incidence of ALS in Europe is 2-3 cases per 100,000 in iduals in the general population, and the overall lifetime risk of developing the disease is 1:400. ALS is familial in 5% of cases, and shows a Mendelian pattern of inheritance. ALS is recognized to overlap with frontotemporal dementia. Diagnosis is made on clinical grounds, using internationally recognized consensus criteria, after exclusion of conditions that can mimic ALS. The Revised ALS Functional Rating Scale is currently the most widely used assessment tool scores are used to predict survival, and have been employed extensively in clinical trials. Riluzole remains the only effective drug, and extends the average survival of patients by 3-6 months. Optimal treatment is based on symptom management and preservation of quality of life, provided in a multidisciplinary setting. The discovery of further effective disease-modifying therapies remains a critical need for patients with this devastating condition.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 10-2014
Publisher: American Association for the Advancement of Science (AAAS)
Date: 27-03-2015
Abstract: Amyotrophic lateral sclerosis (ALS), often referred to as “Lou Gehrig's disease,” is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Cirulli et al. sequenced the expressed genes of nearly 3000 ALS patients and compared them with those of more than 6000 controls (see the Perspective by Singleton and Traynor). They identified several proteins that were linked to disease in patients. One such protein, TBK1, is implicated in innate immunity and autophagy and may represent a therapeutic target. Science , this issue p. 1436 see also p. 1422
Publisher: Elsevier BV
Date: 03-2013
Publisher: Elsevier BV
Date: 2013
Location: United States of America
No related grants have been discovered for Orla Hardiman.