MRC Strategic Award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases
Lead Research Organisation:
UNIVERSITY COLLEGE LONDON
Department Name: Institute of Neurology
Abstract
Neuromuscular Diseases (NMD) affect at least 17 million children and adults globally. They cause either premature death or are chronic diseases causing lifelong disability with economic impact. They include many different disorders affecting muscle and nerve function and account for ~20% of all non-infectious neurological diseases. Examples include muscular dystrophies, congenital myopathies, neuropathies, motor neuron diseases, muscle channelopathies and mitochondrial diseases. Advances in genetics have improved our ability to diagnose patients in the UK, and this has resulted in improved patient care and enabled clinical trials. However the benefits of genetic advances have not been realised in Official Development Assistance (ODA) defined Lower and Middle Income Countries (LMICs), partly because of a lack of neurologists trained specifically in genomic NMD medicine.
NMDs are commonly genetic and are inherited. Identifying genetic pathways and applying genetic testing has led to some of the most important advances in disease understanding alongside patient management plans and the development of new therapies. Many of the key interventions involve the inexpensive practical applications of widely available medical technology (e.g. low-cost off-licence medication, targeted vaccination, cardiac monitoring and respiratory care), but their application is contingent on making a precise diagnosis. For example, a precise genetic diagnosis can lead to a personalised and often simple management plan following established care guidelines that includes basic screening for known complications (e.g. cardiac, respiratory, gastroenterological and metabolic) and often simple interventions that improve health outcomes - interventions that could be implemented easily in LMICs providing an accurate genetic diagnosis is made. In the UK, a muscle biopsy has been the mainstay in the investigation algorithm in many patients, but this requires a specialist laboratory equipped for frozen section analysis with a growing panel of diagnostic antibodies. However, recent advances in genomics provide the opportunity to diagnose with high precision based on a DNA sample and clinical data collected remotely.
Our central objective is to build ethnically diverse cohorts of children and adults with NMDs and undertake genomic analysis to find known and identify new disease genes. We will increase the number of patients with a precise genetic diagnosis to both improve patient care and to increase knowledge on the comparative genetic architecture of NMDs across four continents.
This is a brand new transcontinental programme led by UK professors at UCL, Newcastle and Cambridge Universities. The research programme will train a new generation of academic doctors, generate the world's largest cohort of 15,000 ethnically diverse NMD patients and will investigate the causative genes. We will work with five LMIC clinical and academic centres in: India, Turkey, South Africa, Zambia and Brazil. The trained doctors will be the future clinical academic leaders to undertake research and improve NMD patient care in these countries. The fellows will already be fully trained in neurology and will spend a year in the UK for specialist training in NMD genomic medicine and spend three years in their country building NMD patient cohorts that will be assessed in detail clinically and will undergo full genetic analysis to achieve a precise diagnosis and optimise patient management. All data produced will be anonymised and shared by all researchers. Importantly, we have access to several thousand ethnically matched control DNAs already and will build this control resource further, complementing those available through the Genomics England 100,000 genomes project, the NIHR BioResource and international collaborative resources. We will train a new generation of NMD doctors who will pursue their research career in their own country, discover new genes and improve patient care.
NMDs are commonly genetic and are inherited. Identifying genetic pathways and applying genetic testing has led to some of the most important advances in disease understanding alongside patient management plans and the development of new therapies. Many of the key interventions involve the inexpensive practical applications of widely available medical technology (e.g. low-cost off-licence medication, targeted vaccination, cardiac monitoring and respiratory care), but their application is contingent on making a precise diagnosis. For example, a precise genetic diagnosis can lead to a personalised and often simple management plan following established care guidelines that includes basic screening for known complications (e.g. cardiac, respiratory, gastroenterological and metabolic) and often simple interventions that improve health outcomes - interventions that could be implemented easily in LMICs providing an accurate genetic diagnosis is made. In the UK, a muscle biopsy has been the mainstay in the investigation algorithm in many patients, but this requires a specialist laboratory equipped for frozen section analysis with a growing panel of diagnostic antibodies. However, recent advances in genomics provide the opportunity to diagnose with high precision based on a DNA sample and clinical data collected remotely.
Our central objective is to build ethnically diverse cohorts of children and adults with NMDs and undertake genomic analysis to find known and identify new disease genes. We will increase the number of patients with a precise genetic diagnosis to both improve patient care and to increase knowledge on the comparative genetic architecture of NMDs across four continents.
This is a brand new transcontinental programme led by UK professors at UCL, Newcastle and Cambridge Universities. The research programme will train a new generation of academic doctors, generate the world's largest cohort of 15,000 ethnically diverse NMD patients and will investigate the causative genes. We will work with five LMIC clinical and academic centres in: India, Turkey, South Africa, Zambia and Brazil. The trained doctors will be the future clinical academic leaders to undertake research and improve NMD patient care in these countries. The fellows will already be fully trained in neurology and will spend a year in the UK for specialist training in NMD genomic medicine and spend three years in their country building NMD patient cohorts that will be assessed in detail clinically and will undergo full genetic analysis to achieve a precise diagnosis and optimise patient management. All data produced will be anonymised and shared by all researchers. Importantly, we have access to several thousand ethnically matched control DNAs already and will build this control resource further, complementing those available through the Genomics England 100,000 genomes project, the NIHR BioResource and international collaborative resources. We will train a new generation of NMD doctors who will pursue their research career in their own country, discover new genes and improve patient care.
Technical Summary
We will train a new group of clinical academic fellows to ultimately benefit patients in each partner LMIC. Fellows will be trained to build a cohort of 15,000 Neuromuscular disease (NMD) patients for deep phenotyping and comprehensive genotyping, we will:
(i) Establish an easy to use platform for deep clinical phenotyping and sharing of genome data/results between all project members. We will adopt the pseudo-anonymised, secure and cloud based RD-Connect platform (http://rd-connect.eu/), that uses PhenoTips (https://phenotips.org/) and Human Phenotype Ontology (HPO) (http://human-phenotypeontology.github.io/) terminology. This freely available software platform will be used for each patient/family, entered on secure iPAD locally. This platform allows future collaboration with European and International rare disease initiatives. We will also adopt Open-Clinica for natural history of disease, and later therapeutic trials. This approach ensures cross compatibility with national (GEL, NIHR BioResource) and international efforts (RD-connect).
(ii) Establish a common laboratory framework for high quality DNA extraction from blood, logged and stored in the cloud database following guidelines of UK accredited diagnostic laboratories.
(iii) Establish common genetic screening platform across laboratories, based on a tiering genetic analysis system hierarchy we developed and tested in the UK. This accounts for the molecular test complexity, number of genes and analysis requirements.
(iv) Train fellows in core bioinformatics skills and basic genetic laboratory techniques to ensure an equal skill set in each LMIC.
(v) Employ integrated genomic-phenotype cloud based platform for effective interpretation and gene discovery.
We will identify known and new disease genes, and assess comparative genetic architecture across 4 continents. This will improve understanding of phenotypic variability, disease progression and disease mechanisms, and build "trial ready" cohorts.
(i) Establish an easy to use platform for deep clinical phenotyping and sharing of genome data/results between all project members. We will adopt the pseudo-anonymised, secure and cloud based RD-Connect platform (http://rd-connect.eu/), that uses PhenoTips (https://phenotips.org/) and Human Phenotype Ontology (HPO) (http://human-phenotypeontology.github.io/) terminology. This freely available software platform will be used for each patient/family, entered on secure iPAD locally. This platform allows future collaboration with European and International rare disease initiatives. We will also adopt Open-Clinica for natural history of disease, and later therapeutic trials. This approach ensures cross compatibility with national (GEL, NIHR BioResource) and international efforts (RD-connect).
(ii) Establish a common laboratory framework for high quality DNA extraction from blood, logged and stored in the cloud database following guidelines of UK accredited diagnostic laboratories.
(iii) Establish common genetic screening platform across laboratories, based on a tiering genetic analysis system hierarchy we developed and tested in the UK. This accounts for the molecular test complexity, number of genes and analysis requirements.
(iv) Train fellows in core bioinformatics skills and basic genetic laboratory techniques to ensure an equal skill set in each LMIC.
(v) Employ integrated genomic-phenotype cloud based platform for effective interpretation and gene discovery.
We will identify known and new disease genes, and assess comparative genetic architecture across 4 continents. This will improve understanding of phenotypic variability, disease progression and disease mechanisms, and build "trial ready" cohorts.
Planned Impact
The mission is to create a transcontinental genomics research and capacity building partnership between the UK & India, Turkey, South Africa, Zambia and Brazil. The beneficiaries include:
1) Patients and patient organisations
2) Basic and clinical scientists in neurology, neuroscience and genetics
3) Policy and guidelines
4) Pharmaceutical industry
There are particular challenges faced in the field of NMD which apply across stakeholder groups, and impact in all challenge areas will be achieved through our outputs. Patients and the patient organisations face uncertain access to diagnosis and care, have limited access to clinical trials and the majority are without effective therapies. The clinical and academic groups who work with NMD require resources and know-how to underpin delivery of care and translational research. The policy-makers determine care delivery, and need information on which to base health recommendations. Industrial partners frequently lack knowledge in the disease areas and perceive that the field lacks "trial readiness". By targeting the needs of these distinct stakeholder groups, we will provide outputs which will promote health in this patient group, as well as promoting UK international research competitiveness. Strong relationships are already in place to ensure that impact can be maximised. These include:
1) Key roles for our PIs in national/international patient organisations
2) Strong involvement of our patients and patient organisations in research design and oversight
3) Leading roles of our PIs in host clinical/academic organisations
4) Existing relationships in key areas of liaison with policy makers involved in rare disease public health decision making in UK and LMICs
5) Many links to industry (as detailed in Pathway to Impact)
PATIENTS AND PATIENT ORGANISATIONS: They will benefit from precise genetic diagnosis and cohort stratification enabling trial ready cohorts for the experimental medicine studies and increased trial activity, aimed at defining better therapeutic strategies. Improved diagnostics and treatments will ultimately impact on health, quality of life and societal benefit via greater participation of this patient group in their communities.
CLINICIANS AND ACADEMICS: The clinical and academic groups working with NMD require resources and know-how to deliver care and genomic translational research effectively. Underpinning the experimental medicine potential will be the development of international stratified genetic cohorts, enabling personalised medicine and a much larger group of patients to contribute to experimental clinical studies and access standardised procedures for care and assessment internationally. Training LMIC fellows in genomic medicine will benefit the local academic community and increase research in NMD and benefit patients through more expert clinical care, accurate genetic diagnosis and through "trial ready" cohorts.
POLICY AND GUIDELINES: Policy makers in LMICs who determine care delivery in this area need information on which to base health recommendations. Detailed understanding of prevalence and population specific genetic variations in NMD cohorts, and the important insights these data will provide to NMD patients globally, will aid healthcare policy development. These data will also facilitate development of national and international diagnostic and management guidelines. Policy makers will have access to clearer and more harmonised guidance on the management of these patient groups which can be applied to healthcare planning.
INDUSTRY: Stratified cohorts, research know-how, and a strategic programme of preclinical research provide a conducive environment for increased industry engagement with the presence of trial expertise and ready access to rare patients. We will identify targets for new areas of industrial exploitation.
1) Patients and patient organisations
2) Basic and clinical scientists in neurology, neuroscience and genetics
3) Policy and guidelines
4) Pharmaceutical industry
There are particular challenges faced in the field of NMD which apply across stakeholder groups, and impact in all challenge areas will be achieved through our outputs. Patients and the patient organisations face uncertain access to diagnosis and care, have limited access to clinical trials and the majority are without effective therapies. The clinical and academic groups who work with NMD require resources and know-how to underpin delivery of care and translational research. The policy-makers determine care delivery, and need information on which to base health recommendations. Industrial partners frequently lack knowledge in the disease areas and perceive that the field lacks "trial readiness". By targeting the needs of these distinct stakeholder groups, we will provide outputs which will promote health in this patient group, as well as promoting UK international research competitiveness. Strong relationships are already in place to ensure that impact can be maximised. These include:
1) Key roles for our PIs in national/international patient organisations
2) Strong involvement of our patients and patient organisations in research design and oversight
3) Leading roles of our PIs in host clinical/academic organisations
4) Existing relationships in key areas of liaison with policy makers involved in rare disease public health decision making in UK and LMICs
5) Many links to industry (as detailed in Pathway to Impact)
PATIENTS AND PATIENT ORGANISATIONS: They will benefit from precise genetic diagnosis and cohort stratification enabling trial ready cohorts for the experimental medicine studies and increased trial activity, aimed at defining better therapeutic strategies. Improved diagnostics and treatments will ultimately impact on health, quality of life and societal benefit via greater participation of this patient group in their communities.
CLINICIANS AND ACADEMICS: The clinical and academic groups working with NMD require resources and know-how to deliver care and genomic translational research effectively. Underpinning the experimental medicine potential will be the development of international stratified genetic cohorts, enabling personalised medicine and a much larger group of patients to contribute to experimental clinical studies and access standardised procedures for care and assessment internationally. Training LMIC fellows in genomic medicine will benefit the local academic community and increase research in NMD and benefit patients through more expert clinical care, accurate genetic diagnosis and through "trial ready" cohorts.
POLICY AND GUIDELINES: Policy makers in LMICs who determine care delivery in this area need information on which to base health recommendations. Detailed understanding of prevalence and population specific genetic variations in NMD cohorts, and the important insights these data will provide to NMD patients globally, will aid healthcare policy development. These data will also facilitate development of national and international diagnostic and management guidelines. Policy makers will have access to clearer and more harmonised guidance on the management of these patient groups which can be applied to healthcare planning.
INDUSTRY: Stratified cohorts, research know-how, and a strategic programme of preclinical research provide a conducive environment for increased industry engagement with the presence of trial expertise and ready access to rare patients. We will identify targets for new areas of industrial exploitation.
Organisations
- UNIVERSITY COLLEGE LONDON (Lead Research Organisation, Project Partner)
- KING'S COLLEGE LONDON (Collaboration)
- Folkhalsan Research Centre (Collaboration)
- Centre for Genomic Regulation - CGR (Project Partner)
- Guarantors of Brain (Project Partner)
- Newcastle University (Project Partner)
- Centre for DNA Fingerprinting & Diagnost (Project Partner)
- University of Miami (Project Partner)
- World Muscle Society (WMS) (Project Partner)
- NIHR Cambridge Biomedical Research Ctr (Project Partner)
- Genomics England (Project Partner)
- Leiden University Medical Centre (Project Partner)
Publications
Ferreira T
(2024)
Variants in mitochondrial disease genes are common causes of inherited peripheral neuropathies.
in Journal of neurology
Sung A
(2024)
Systematic analysis of NDUFAF6 in complex I assembly and mitochondrial disease
in Nature Metabolism
Pipis M
(2024)
Nerve biopsy in T-cell lymphoma with neurolymphomatosis: where and when.
in Practical neurology
Tomaselli PJ
(2024)
Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A.
in European journal of neurology
Lemmers RJLF
(2024)
Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy.
in Brain : a journal of neurology
Kaiyrzhanov R
(2024)
Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.
in Movement disorders : official journal of the Movement Disorder Society
Muthukumarasamy M
(2024)
TTR associated leptomeningeal amyloidosis in a Sri Lankan patient.
in Journal of the neurological sciences
Raga S
(2024)
Paediatric neuromuscular diseases in Africa: access to care.
in Neuromuscular disorders : NMD
Maroofian R
(2024)
RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.
in Brain : a journal of neurology
Frezatti RSS
(2024)
Overcoming genetic neuromuscular diagnostic pitfalls in a middle-income country.
in Brain communications
Doherty C
(2024)
Lower limb muscle MRI fat fraction is a responsive outcome measure in CMT X1 , 1B and 2A
in Annals of Clinical and Translational Neurology
Figueiredo FB
(2024)
Genetic diversity in hereditary axonal neuropathy: Analyzing 53 Brazilian children.
in Journal of the peripheral nervous system : JPNS
Gomathy Saranya B.
(2024)
Phenotypic, Electrophysiologic, and Imaging Spectrum of Hirayama Disease from Northern India
in ANNALS OF INDIAN ACADEMY OF NEUROLOGY
Chelban V
(2024)
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
in Nature Communications
O'Donnell LF
(2024)
Quantitative MRI outcome measures in CMT1A using automated lower limb muscle segmentation.
in Journal of neurology, neurosurgery, and psychiatry
Efthymiou Stephanie
(2024)
Novel bi-allelic TRMT1 variants perturb tRNA modifications expanding the clinical spectrum of intellectual disability
in EUROPEAN JOURNAL OF HUMAN GENETICS
Olimpio C
(2024)
Increased Diagnostic Yield by Reanalysis of Whole Exome Sequencing Data in Mitochondrial Disease.
in Journal of neuromuscular diseases
Dudziec MM
(2024)
Home-based multi-sensory and proximal strengthening program to improve balance in Charcot-Marie-Tooth disease Type 1A: A proof of concept study.
in Muscle & nerve
Paß T
(2024)
Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons.
in Brain : a journal of neurology
Horton RH
(2024)
Discussion of off-target and tentative genomic findings may sometimes be necessary to allow evaluation of their clinical significance.
in Journal of medical ethics
Henning F
(2024)
Extended Phenotype of PEX11B Pathogenic Variants: Ataxia, Tremor, and Dystonia Due to a Novel C.2T > G Variant.
in Movement disorders clinical practice
Podmanicky O
(2024)
Mitochondrial aminoacyl-tRNA synthetases trigger unique compensatory mechanisms in neurons.
in Human molecular genetics
Correia SP
(2024)
Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease.
in JCI insight
Harel T
(2024)
De novo variants in ATXN7L3 lead to developmental delay, hypotonia and distinctive facial features.
in Brain : a journal of neurology
Brunet T
(2024)
De novo variants in RNF213 are associated with a clinical spectrum ranging from Leigh syndrome to early-onset stroke.
in Genetics in medicine : official journal of the American College of Medical Genetics
Murley AG
(2024)
7T MRI detects widespread brain iron deposition in neuroferritinopathy.
in Annals of clinical and translational neurology
Mancuso M
(2024)
Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.
in European journal of neurology
Efthymiou S
(2024)
Human mutations in SLITRK3 implicated in GABAergic synapse development in mice.
in Frontiers in molecular neuroscience
Male AJ
(2024)
Acceptability of Audiovestibular Assessment in the Home-A Patient Survey.
in Audiology research
Nagy S
(2024)
Autosomal recessive VWA1-related disorder: comprehensive analysis of phenotypic variability and genetic mutations.
in Brain communications
Bisschoff M
(2024)
Clinical, biochemical, and genetic spectrum of MADD in a South African cohort: an ICGNMD study.
in Orphanet journal of rare diseases
Hikmat O
(2024)
Status epilepticus in POLG disease: a large multinational study.
in Journal of neurology
Ratnaike T
(2024)
Evidence for sodium valproate toxicity in mitochondrial diseases: a systematic analysis
in BMJ Neurology Open
Major T
(2024)
Correlation Between the SARA and A-T NEST Clinical Severity Scores in Adults with Ataxia-Telangiectasia.
in Cerebellum (London, England)
Van Haute L
(2025)
Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease.
in EMBO molecular medicine
Laugwitz L
(2025)
EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.
in American journal of human genetics
O'Connor A
(2025)
Genetic testing in dementia.
in Practical neurology
Falabella M
(2025)
Biallelic PTPMT1 variants disrupt cardiolipin metabolism and lead to a neurodevelopmental syndrome.
in Brain : a journal of neurology
Pizzamiglio C
(2025)
Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease.
in Brain : a journal of neurology
Tiet M
(2025)
Novel observation for adult ataxia-telangiectasia: evaluating the lack of hypointensity of the dentate nuclei
in Journal of Neurology, Neurosurgery & Psychiatry
Carvalho G
(2025)
Activating AMPK improves pathological phenotypes due to mtDNA depletion.
in The FEBS journal
Schoonen M
(2025)
Biallelic variants in RYR1 and STAC3 are predominant causes of King-Denborough Syndrome in an African cohort.
in European journal of human genetics : EJHG
Zhang K
(2025)
Human TRMT1 and TRMT1L paralogs ensure the proper modification state, stability, and function of tRNAs.
in Cell reports
Cortese A
(2025)
Genotype and phenotype spectrum of Charcot-Marie-Tooth disease due to mutations in SORD.
in Brain : a journal of neurology
| Title | Additional file 1 of Prevalence of familial cluster headache: a systematic review and meta-analysis |
| Description | Additional file 1: Supplementary Figure 1. Density plot confirming normality following transformation of data. |
| Type Of Art | Image |
| Year Produced | 2020 |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Prevalence_of_familial_cluster_hea... |
| Title | Additional file 2 of Prevalence of familial cluster headache: a systematic review and meta-analysis |
| Description | Additional file 2: Supplementary Figure 2. Analysis involved random effects model which included all the identified studies estimating the prevalence of family history. |
| Type Of Art | Image |
| Year Produced | 2020 |
| URL | https://springernature.figshare.com/articles/Additional_file_2_of_Prevalence_of_familial_cluster_hea... |
| Title | Additional file 3 of Prevalence of familial cluster headache: a systematic review and meta-analysis |
| Description | Additional file 3: Supplementary Figure 3. Diagnostic plots indicating the presence of an outlier in the estimation of relative proportion of effected probands with positive family history of CH. |
| Type Of Art | Image |
| Year Produced | 2020 |
| URL | https://springernature.figshare.com/articles/Additional_file_3_of_Prevalence_of_familial_cluster_hea... |
| Description | A Lily Precision Diagnostic Service - Accelerating the Introduction of Advanced Diagnostics for Mitochondrial Patients in the NHS |
| Amount | £644,882 (GBP) |
| Organisation | The Lily Foundation |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 02/2027 |
| Description | BRC3 |
| Amount | £25,000 (GBP) |
| Organisation | University College Hospital |
| Sector | Hospitals |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 09/2022 |
| Description | Centre to Treat Mitochondrial Diseases |
| Amount | £7,585,750 (GBP) |
| Organisation | LifeArc |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2024 |
| End | 09/2029 |
| Description | Developing an advanced therapy platform for neurological diseases |
| Amount | £3,530,000 (GBP) |
| Organisation | University College Hospital |
| Sector | Hospitals |
| Country | United Kingdom |
| Start | |
| Description | Indian Council of Medical Research (ICMR) research grant to All India Institute of Medical Sciences (Delhi): Identification of the Genetic architecture of Facioscapulohumeral muscular dystrophy in India |
| Amount | ₹836,422,659 (INR) |
| Organisation | Indian Council of Medical Research (ICMR) |
| Sector | Public |
| Country | India |
| Start | 05/2023 |
| End | 06/2026 |
| Description | Investigating the role of cardiolipin metabolism in mitochondrial DNA replication and mitochondrial division |
| Amount | £1,083,602 (GBP) |
| Funding ID | MR/S002065/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2019 |
| End | 02/2024 |
| Description | Joint Seed Fund Call |
| Amount | £5,000 (GBP) |
| Organisation | University College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 07/2022 |
| Description | MDUK support for the LifeArc Centre to Treat Mitochondrial Disorders (LAC-TreatMito) |
| Amount | £1,142,945 (GBP) |
| Funding ID | 23SI-PRG60-0013 |
| Organisation | Muscular Dystrophy UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2024 |
| End | 08/2029 |
| Description | MitoCluster Consortium : An Integrated Phenotyping and Mouse Model Generation Platform for Mitochondrial Disease and Dysfunction |
| Amount | £2,933,088 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 02/2029 |
| Description | MitoCluster: an integrated phenotyping and mouse model generation platform for mitochondrial disease and dysfunction |
| Amount | £2,933,088 (GBP) |
| Funding ID | MC_PC_21046 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 03/2027 |
| Description | Neuromuscular Clinical Trial Coordinator |
| Amount | £56,294 (GBP) |
| Organisation | National Brain Appeal |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2019 |
| End | 11/2020 |
| Description | Neuromuscular Disease Theme 3 |
| Amount | £257,408 (GBP) |
| Organisation | University College Hospital |
| Sector | Hospitals |
| Country | United Kingdom |
| Start | 03/2020 |
| End | 05/2022 |
| Description | Neuromuscular Research Manager |
| Amount | £200,312 (GBP) |
| Organisation | National Brain Appeal |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2019 |
| End | 05/2024 |
| Description | TransNAT: Transforming delivery, safety, and efficacy of nucleic acid therapeutics; from intracellular uptake to targeting brain, heart and muscle |
| Amount | £1,777,003 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 09/2025 |
| Description | UCL:AIIMS Intramural award: The first investigation of the genetic causes of Facioscapulohumeral muscular dystrophy (FSHD) in the Indian population |
| Amount | £10,000 (GBP) |
| Funding ID | UCL:AIIMS collaborative seed funding awards (Global Engagement) |
| Organisation | University College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 06/2023 |
| Title | Additional file 1 of Clinical implementation of RNA sequencing for Mendelian disease diagnostics |
| Description | Additional file 1: Table S1. Sample annotation. Table S2. Extended summary of RNA-seq diagnosed cases. Table S3. Summary of candidate genes pinpointed via RNA-seq. Table S4. Summary of WES-diagnosed cases with an RNA-defect. Table S5. Recalled expression outliers at different mean and dispersion. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Clinical_implementation_of... |
| Title | Quadruple immunofluoresence images of skeletal muscle biopsies from patients with the mtDNA m.3243A>G variant |
| Description | Fluorescent images of 10µm transverse muscle sections from patients carrying the pathogenic m.3243A>G mtDNA variant, captured by automated scanning at 20× magnification using Zen 2011 (blue edition) software and Zeiss Axio imager MI microscope. Exposure times across all sections for each experimental batch were maintained. Muscle sections were stained using a 'Quantitative quadruple immunohistochemistry' technique, designed to capture expression profiles of proteins belonging to oxidative phosphorylation (OXPHOS) complexes. 'OXPHOS' sections were labelled with antibodies detecting subunits of mitochondrial complex I (NDUFB8) and complex IV (COX-1), a mitochondrial mass marker (mitochondrial porin; VDAC1) and laminin, followed by incubation with secondary antibodies (Alexa Fluor 488, 546, biotinylated IgG1 and 750) and subsequently with streptavidin 647. Alongside each sample, a no-primary control section (NPC; labelled only for laminin) was processed. This resource contains .iaf, .jpg and .png files from OXPHOS and NPC sections from 17 patients (P01-P17) and five controls (C01-C05). It also contains PDFs for 10 sections for which single fibre molecular genetic data are available at https://github.com/CnrLwlss/Ahmed_2022 File naming convention: b : where n=2 or 3 and refers to the batch that the samples were processed in. P01-P17 : Sections from m.3243A>G patients C01-C05 : Non-disease controls NPC : Non-primary control - sections labelled only with laminin OXPHOS : Sections labelled for OXPHOS complexes ch1 : MTCO1 (Complex IV; 488nm) ch2 : VDAC (Porin; 546nm) ch3 : NDUFB8 (Complex I; 647nm) ch4 : Laminin (750nm) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://data.ncl.ac.uk/articles/dataset/Quadruple_immunofluoresence_images_of_skeletal_muscle_biopsi... |
| Title | Quadruple immunofluoresence images of skeletal muscle biopsies from patients with the mtDNA m.3243A>G variant |
| Description | Fluorescent images of 10µm transverse muscle sections from patients carrying the pathogenic m.3243A>G mtDNA variant, captured by automated scanning at 20× magnification using Zen 2011 (blue edition) software and Zeiss Axio imager MI microscope. Exposure times across all sections for each experimental batch were maintained. Muscle sections were stained using a 'Quantitative quadruple immunohistochemistry' technique, designed to capture expression profiles of proteins belonging to oxidative phosphorylation (OXPHOS) complexes. 'OXPHOS' sections were labelled with antibodies detecting subunits of mitochondrial complex I (NDUFB8) and complex IV (COX-1), a mitochondrial mass marker (mitochondrial porin; VDAC1) and laminin, followed by incubation with secondary antibodies (Alexa Fluor 488, 546, biotinylated IgG1 and 750) and subsequently with streptavidin 647. Alongside each sample, a no-primary control section (NPC; labelled only for laminin) was processed. This resource contains .iaf, .jpg and .png files from OXPHOS and NPC sections from 17 patients (P01-P17) and five controls (C01-C05). It also contains PDFs for 10 sections for which single fibre molecular genetic data are available at https://github.com/CnrLwlss/Ahmed_2022 File naming convention: b : where n=2 or 4 and refers to the batch that the samples were processed in. Some samples have been processed twice, in two separate batches. P01-P17 : Sections from m.3243A>G patients C01-C05 : Non-disease controls NPC : Non-primary control - sections labelled only with laminin OXPHOS : Sections labelled for OXPHOS complexes ch1 : MTCO1 (Complex IV; 488nm) ch2 : VDAC (Porin; 546nm) ch3 : NDUFB8 (Complex I; 647nm) ch4 : Laminin (750nm) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://data.ncl.ac.uk/articles/dataset/Quadruple_immunofluoresence_images_of_skeletal_muscle_biopsi... |
| Title | Quadruple immunofluoresence images of skeletal muscle biopsies from patients with the mtDNA m.3243A>G variant |
| Description | Fluorescent images of 10µm transverse muscle sections from patients carrying the pathogenic m.3243A>G mtDNA variant, captured by automated scanning at 20× magnification using Zen 2011 (blue edition) software and Zeiss Axio imager MI microscope. Exposure times across all sections for each experimental batch were maintained. Muscle sections were stained using a 'Quantitative quadruple immunohistochemistry' technique, designed to capture expression profiles of proteins belonging to oxidative phosphorylation (OXPHOS) complexes. 'OXPHOS' sections were labelled with antibodies detecting subunits of mitochondrial complex I (NDUFB8) and complex IV (COX-1), a mitochondrial mass marker (mitochondrial porin; VDAC1) and laminin, followed by incubation with secondary antibodies (Alexa Fluor 488, 546, biotinylated IgG1 and 750) and subsequently with streptavidin 647. Alongside each sample, a no-primary control section (NPC; labelled only for laminin) was processed. This resource contains .iaf, .jpg and .png files from OXPHOS and NPC sections from 17 patients (P01-P17) and five controls (C01-C05). It also contains PDFs for 10 sections for which single fibre molecular genetic data are available at https://github.com/CnrLwlss/Ahmed_2022 File naming convention: b : where n=2 or 4 and refers to the batch that the samples were processed in. Some samples have been processed twice, in two separate batches. P01-P17 : Sections from m.3243A>G patients C01-C05 : Non-disease controls NPC : Non-primary control - sections labelled only with laminin OXPHOS : Sections labelled for OXPHOS complexes ch1 : MTCO1 (Complex IV; 488nm) ch2 : VDAC (Porin; 546nm) ch3 : NDUFB8 (Complex I; 647nm) ch4 : Laminin (750nm) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | https://data.ncl.ac.uk/articles/dataset/Quadruple_immunofluoresence_images_of_skeletal_muscle_biopsi... |
| Description | Titinopathy and Nebulin myopathy collaboration between ICGNMD & Folkhälsan Research Center, Helsinki |
| Organisation | Folkhalsan Research Centre |
| Country | Finland |
| Sector | Charity/Non Profit |
| PI Contribution | ICGNMD collaborates with the Professor Bjarne Udd and Dr Marco Savarese to discuss relevance of mutations in the Titin gene present in the ICGNMD cohort, and with Professor Vilma Lehtokari, Professor Carina Wallgren and Dr Katarina Pelin to discuss mutations in the Nebulin gene. |
| Collaborator Contribution | ICGNMD provides anonymised genetic and clinical data and discusses the significance of Titin and Nebulin gene variants with the team in Helsinki, who have specialist expertise. |
| Impact | The collaboration is new so there are no formal outputs yet. |
| Start Year | 2023 |
| Description | Titinopathy collaboration between ICGNMD & King's College, London |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | ICGNMD has established a new collaboration with titinopathy experts at King's College London to facilitate analysis of TTN variants found through ICGNMD genetic testing. |
| Collaborator Contribution | The partnership is new but partners will bring titinopathy expertise in the future. |
| Impact | New collaboration, no outputs as yet. |
| Start Year | 2024 |