Christopher E. Shaw
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View article: U7 small nuclear RNA splice-switching therapeutics for STMN2 and UNC13A in Amyotrophic Lateral Sclerosis
U7 small nuclear RNA splice-switching therapeutics for STMN2 and UNC13A in Amyotrophic Lateral Sclerosis Open
TDP-43 nuclear depletion in amyotrophic lateral sclerosis (ALS) causes de-repression of cryptic exons (CEs) in multiple transcripts, including UNC13A and STMN2 , disrupting synaptic transmission and neurite outgrowth. We developed a therap…
View article: Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia
Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia Open
GRN mutations leading to progranulin haploinsufficiency can cause frontotemporal dementia. AVB-101, an investigational gene therapy comprising an adeno-associated virus construct expressing codon-optimized human GRN under a n…
View article: Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules
Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules Open
View article: Towards a diagnostic test for sporadic ALS utilising deep learning and SNP microarrays
Towards a diagnostic test for sporadic ALS utilising deep learning and SNP microarrays Open
A variety of common and rare genetic factors have been implicated in the development of amyotrophic lateral sclerosis (ALS), and the evidence is that a genetic component is present in most affected individuals. However, our current underst…
View article: Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications
Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications Open
Background Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case–control statistical evidence implicating oligogenicity with disease risk or clinical outcomes is limited. Consider…
View article: Pre‐clinical development of AVB‐101, an AAV gene therapy treatment for frontotemporal dementia with progranulin mutations
Pre‐clinical development of AVB‐101, an AAV gene therapy treatment for frontotemporal dementia with progranulin mutations Open
Background Frontotemporal dementia (FTD) presents with a change in personality, behaviour and language and is the second most common cause of young‐onset dementia after Alzheimer’s disease. Loss of function mutations in GRN , encoding prog…
View article: Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis
Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis Open
Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron dis…
View article: Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data
Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data Open
Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neurona…
View article: Author Correction: The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
Author Correction: The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration Open
View article: Mutations in the tail and rod domains of the neurofilament heavy‐chain gene increase the risk of <scp>ALS</scp>
Mutations in the tail and rod domains of the neurofilament heavy‐chain gene increase the risk of <span>ALS</span> Open
Objective Neurofilament heavy‐chain gene ( NEFH ) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening …
View article: Computing linkage disequilibrium aware genome embeddings using autoencoders
Computing linkage disequilibrium aware genome embeddings using autoencoders Open
Motivation The completion of the genome has paved the way for genome-wide association studies (GWAS), which explained certain proportions of heritability. GWAS are not optimally suited to detect non-linear effects in disease risk, possibly…
View article: Hippocampal aggregation signatures of pathogenic <i>UBQLN2</i> in amyotrophic lateral sclerosis and frontotemporal dementia
Hippocampal aggregation signatures of pathogenic <i>UBQLN2</i> in amyotrophic lateral sclerosis and frontotemporal dementia Open
Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterized by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus and spinal cord. However, ubiqu…
View article: The oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling, and therapeutic implications
The oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling, and therapeutic implications Open
Recently, large-scale case-control analyses have been prioritized in the study of ALS. Yet the same effort has not been put forward to investigate additive moderate phenotypic effects of genetic variants in genes driving ALS risk, despite …
View article: Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS
Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS Open
Gene supplementation and editing for neurodegenerative disorders has emerged in recent years as the understanding of the genetic mechanisms underlying several neurodegenerative disorders increases. The most common medium to deliver genetic…
View article: Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons
Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons Open
Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disorder characterized by progressive muscular weakness due to the selective loss of motor neurons. Mutations in the gene Fused in Sarcoma (FUS) were identified …
View article: PB0146 Functional Characterization of a Human F9 Gene-Inserted Product in Hemophilia B Mice
PB0146 Functional Characterization of a Human F9 Gene-Inserted Product in Hemophilia B Mice Open
View article: SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in <i>SOD1</i> amyotrophic lateral sclerosis
SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in <i>SOD1</i> amyotrophic lateral sclerosis Open
Objective: Variants in the superoxide dismutase (SOD1) gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to…
View article: Genetic and phenotype analyses of primary lateral sclerosis datasets from international cohorts
Genetic and phenotype analyses of primary lateral sclerosis datasets from international cohorts Open
Primary lateral sclerosis (PLS) is the rarest form of motor neurone disease (MND). It is characterized by upper motor neuron degeneration, leading to progressive weakness, spasticity and functional disability. Although PLS does not typical…
View article: Unsupervised machine-learning identifies clinically distinct subtypes of ALS that reflect different genetic architectures and biological mechanisms
Unsupervised machine-learning identifies clinically distinct subtypes of ALS that reflect different genetic architectures and biological mechanisms Open
Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a highly variable clinical presentation and multifaceted genetic and biological bases that translate into great patient heterogeneity. The…
View article: Generation of an Open-Access Patient-Derived iPSC Biobank for Amyotrophic Lateral Sclerosis Disease Modelling
Generation of an Open-Access Patient-Derived iPSC Biobank for Amyotrophic Lateral Sclerosis Disease Modelling Open
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, causing patients to lose control over voluntary movement, and leading to gradual paralysis and death. There is no c…
View article: Genetic variability in sporadic amyotrophic lateral sclerosis
Genetic variability in sporadic amyotrophic lateral sclerosis Open
With the advent of gene therapies for amyotrophic lateral sclerosis (ALS), there is a surge in gene testing for this disease. Although there is ample experience with gene testing for C9orf72, SOD1, FUS and TARDBP in familial ALS, large stu…
View article: The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases
The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases Open
View article: SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in<i>SOD1</i>amyotrophic lateral sclerosis
SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in<i>SOD1</i>amyotrophic lateral sclerosis Open
Objective Variants in the superoxide dismutase ( SOD1 ) gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has…
View article: Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival
Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival Open
Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). …
View article: Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans
Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans Open
View article: Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data
Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data Open
Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respira…
View article: Molecular dynamics analysis of Superoxide Dismutase 1 mutations suggests decoupling between mechanisms underlying ALS onset and progression
Molecular dynamics analysis of Superoxide Dismutase 1 mutations suggests decoupling between mechanisms underlying ALS onset and progression Open
Mutations in the superoxide dismutase 1 ( SOD1 ) gene are the second most common known cause of ALS. SOD1 variants express high phenotypic variability and over 200 have been reported in people with ALS. Investigating how different SOD1 var…
View article: The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration Open
View article: Large-scale Analyses of CAV1 and CAV2 Suggest Their Expression is Higher in Post-mortem ALS Brain Tissue and Affects Survival
Large-scale Analyses of CAV1 and CAV2 Suggest Their Expression is Higher in Post-mortem ALS Brain Tissue and Affects Survival Open
Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in ALS. Disease-associated variants have been identifi…
View article: Mutations in the tail domain of the neurofilament heavy chain gene increase the risk of amyotrophic lateral sclerosis
Mutations in the tail domain of the neurofilament heavy chain gene increase the risk of amyotrophic lateral sclerosis Open
Objective Genetic variation in the neurofilament heavy chain gene ( NEFH ) has been convincingly linked to the pathogenesis of multiple neurodegenerative diseases, however, the relationship between NEFH mutations and ALS susceptibility has…