Predictive measures to stratify clinical outcomes in children and adults with Gaucher disease and responses to specific therapies
Lead Research Organisation:
University of Cambridge
Department Name: Medicine
Abstract
The overall aim is to improve the management of patients with Gaucher disease - a genetic disorder with very variable manifestations, but which causes disabling disease especially in the bones of the skeleton and affects the brain. Advances in biotechnology have introduced specific treatments: there are five licensed therapies manufactured by four companies which work in two distinct ways: formerly bone marrow transplantation (with high mortality) was used. Despite introduction of these high-cost therapies, many patients have persistent symptoms and suffer a long-term risk of bone injury, bone cancer and brain diseases such as Parkinson's. The exact reasons for this are unknown, but there is a clear need for improvement.
To achieve our aim, we will bring key practitioners for the treatment of Gaucher disease, who are based in highly specialized national centres, together in a comprehensive research consortium. We will also bring clinical scientists from academic institutions and commercial academic sectors together in the mission to improve the outcomes of treatment by better targeting and timing of therapy, and to build a starting point for the design of specific trials in an effort to improve health outcomes for Gaucher patients. We work closely in the consortium with major industrial partners, who will bring their unique expertise in line with our clinical and laboratory work and the entire project will be partnered with patient advocacy groups and international societies in this field.
Much of the specific scientific work of this consortium will be built on a comprehensive database reflecting the disease severity and manifestations of Gaucher disease in the entire national cohort of adults and children who suffer. Medical Researchers and specialized nurses will examine individual patients who have consented ethically to the study and from whom blood and other appropriate samples will be obtained and stored centrally for analysis. The data resource will be fully computerized, which will allow sophisticated analysis of the categories of disease and its behaviour to be aligned to additional information about the genetics of the condition and other variables obtained by laboratory measurement. The patients will be re-examined and clinical information obtained retrospectively about key events in their illness will be entered so that its course before and after various treatments can be described and, ultimately characterized. We are looking to define groups of patients who respond well or less well to specific therapies and whose disease progress can be characterized as 'stormy', 'sizzlers' or 'fizzlers'. We already have a range of treatments that have been authorized for prescription (because this is a rare disease they are 'high cost') and also a range of what are referred to as 'biomarkers' which may well be able to predict responses to treatment or serve as a target for when disease is controlled by therapy and complications are unlikely to occur. In the team of Investigators working alongside the UK clinical centres, there are biologists who will explore the role of these biomarkers in relation to disease behaviour so that the targeting of therapy, the best time to use it can be improved and that disease monitoring will be refined in further trials of innovative drugs. In this way, the groups 'cohorts' of patients stratified according to disease severity and behaviour will serve as an attractive platform for investment in clinical trials by the major biopharmaceutical companies. Technology companies will also be attracted to develop diagnostic kits using the biomarkers we discover to improve prognosis. Although rare, Gaucher disease promises unique insights into little-understood conditions that commonly affect the whole population. Large corporations (eg Sanofi) have been attracted to the field, and the key discoveries of the consortium will engage them strategically for future investment and health development.
To achieve our aim, we will bring key practitioners for the treatment of Gaucher disease, who are based in highly specialized national centres, together in a comprehensive research consortium. We will also bring clinical scientists from academic institutions and commercial academic sectors together in the mission to improve the outcomes of treatment by better targeting and timing of therapy, and to build a starting point for the design of specific trials in an effort to improve health outcomes for Gaucher patients. We work closely in the consortium with major industrial partners, who will bring their unique expertise in line with our clinical and laboratory work and the entire project will be partnered with patient advocacy groups and international societies in this field.
Much of the specific scientific work of this consortium will be built on a comprehensive database reflecting the disease severity and manifestations of Gaucher disease in the entire national cohort of adults and children who suffer. Medical Researchers and specialized nurses will examine individual patients who have consented ethically to the study and from whom blood and other appropriate samples will be obtained and stored centrally for analysis. The data resource will be fully computerized, which will allow sophisticated analysis of the categories of disease and its behaviour to be aligned to additional information about the genetics of the condition and other variables obtained by laboratory measurement. The patients will be re-examined and clinical information obtained retrospectively about key events in their illness will be entered so that its course before and after various treatments can be described and, ultimately characterized. We are looking to define groups of patients who respond well or less well to specific therapies and whose disease progress can be characterized as 'stormy', 'sizzlers' or 'fizzlers'. We already have a range of treatments that have been authorized for prescription (because this is a rare disease they are 'high cost') and also a range of what are referred to as 'biomarkers' which may well be able to predict responses to treatment or serve as a target for when disease is controlled by therapy and complications are unlikely to occur. In the team of Investigators working alongside the UK clinical centres, there are biologists who will explore the role of these biomarkers in relation to disease behaviour so that the targeting of therapy, the best time to use it can be improved and that disease monitoring will be refined in further trials of innovative drugs. In this way, the groups 'cohorts' of patients stratified according to disease severity and behaviour will serve as an attractive platform for investment in clinical trials by the major biopharmaceutical companies. Technology companies will also be attracted to develop diagnostic kits using the biomarkers we discover to improve prognosis. Although rare, Gaucher disease promises unique insights into little-understood conditions that commonly affect the whole population. Large corporations (eg Sanofi) have been attracted to the field, and the key discoveries of the consortium will engage them strategically for future investment and health development.
Technical Summary
To build a research consortium that will promote discovery and improve outcomes for patients with Gaucher disease, our overarching aim is to refine treatment using clinical stratification and severity categories based on therapeutic responses. Life-quality is impaired, survival is reduced and crippling skeletal disease, marrow failure, visceromegaly, cancers with disabling neurological effects, including late-onset Parkinsonism, supervene. Disease discrepant between siblings and identical twins, shows that clinical and treatment responses are not determined by genotype alone: in-depth phenotyping is critical for stratification and therapeutic advance. National specialized centres for Gaucher disease will recruit at least 85% of UK patients (~250) with a focus on neurological and osseous disease as research strands in major areas of disability in adults and children. Stratification will facilitate generation of a dynamic platform for advancing therapy and further understanding of disease causation. High-resolution stratification into clinical cohorts will use validated disease severity and life-quality scores to annotate therapeutic responses; we will explore the predictive value of the activated inflammasome and bioactive lipids, as well as established plasma enzymatic and chemokine biomarkers. Partner biostatisticians (MRC external staff) will conduct time-to-event and regression modelling analyses to develop treatment cohorts based on dosing studies (enzyme therapies) and stage of intervention; serial biological samples will be stored and data entered on the custom-designed central national Gaucher register accessed at all centres. Genzyme-Sanofi, Shire HGT and Actelion Pharmaceuticals will share expertise, registry data and key resources; success in building the consortium will render stratified patient cohorts in national Gaucher centres highly attractive for innovative clinical trials and commercial development of predictive and diagnostic biomarker toolkits.
Planned Impact
At least one innovative agent, a small molecule of great potency as a substrate synthesis inhibitor, is in clinical trial in Gaucher disease (eliglustat tartrate - Genzyme-Sanofi): its development was stimulated by the licensing and subsequent approval of the first drug in this class for Gaucher disease, miglustat (Actelion) - a scientific initiative driven almost entirely by the Co-Applicant and Lead Applicant of this proposal. The timespan for progressing drugs to market through such a process is relatively short for Gaucher disease and its congeners, since it benefits from the legislation for orphan medicinal products. Clearly careful stratification to understand the determinants of neurological disease in this national cohort of Gaucher patients would stimulate further investment in small molecules currently in the pipeline for chronic neuronopathic Gaucher disease and related disabilities caused by sphingoliposes affecting the brain such as Tay-Sachs disease.
The maintenance of impact depends upon a combination of clinical need, scientific progress and commercial considerations. Therefore, despite our existing track record of impact, we see a major need to drive the proposed work of this consortium. The role of our research is not to compete head-to-head with the resources available to biopharmaceutical or industrial programmes, which are huge. Instead we aim to support their fragile viability, which can be readily lost by a commercial entity (as nearly occurred with Genzyme's catastrophic vesiviral contamination of the bioreactors serving the manufacture of its key 'blockbuster' enzyme products from 2009) by upgrading the company's investment in science beyond the de-incentivised post-authorization life-cycle phase: developing new diagnostic tools as adjuncts to prognosis and efficacy, and, as here, defining new targets for parallel approaches.
The Council's initiative is likely to have salutary effects on: (1) persistent major illness or disability in our patients (2) the critical gap in scientific and mechanistic understanding of the clinical behaviour of the disease (3) companies and regulatory authorities who need tools to meet the expectation of regulatory authorities for commensurate long-term efficacy and safety, and thereby generate a competitive need for their organizations to show commitment to deeper clinical research (4) biopharmaceutical research plans after licensing where the presence of five licensed (four approved) therapies in Western Europe is inimical to the conduct of naïve blinded and controlled clinical trials and (5) because the mission of the consortium project engenders an unconventional multi-disciplinary and collaborative approach which should stimulate therapeutic discovery and technical spin-off development, for example, in assay kits for newly discovered prognostic biomarkers.
The consortium includes many of the key practitioners in the treatment of Gaucher disease and this project is very much about directly improving the quality of the care they provide. The proposed project aims to improve therapeutic outcomes and targeting, develop better trials, and introduce new prognostic diagnostics and, where possible, innovative therapies.
Outside the consortium, the clinical scientists from both the commercial academic sectors in this field use the academic literature as a key route by which they their own patient care, making academic publication is a key mechanism by which the impact of this research will be delivered. This will be supplemented by the engagement with patient groups and international societies in the field.
Close engagement with the companies who have joined the consortium means that there is a direct link to the providers of medicines to Gaucher patients. Through the open exchange of knowledge across the consortium, these companies can use to the research to develop new therapies and predictive methods based on improved understanding of the disease population.
The maintenance of impact depends upon a combination of clinical need, scientific progress and commercial considerations. Therefore, despite our existing track record of impact, we see a major need to drive the proposed work of this consortium. The role of our research is not to compete head-to-head with the resources available to biopharmaceutical or industrial programmes, which are huge. Instead we aim to support their fragile viability, which can be readily lost by a commercial entity (as nearly occurred with Genzyme's catastrophic vesiviral contamination of the bioreactors serving the manufacture of its key 'blockbuster' enzyme products from 2009) by upgrading the company's investment in science beyond the de-incentivised post-authorization life-cycle phase: developing new diagnostic tools as adjuncts to prognosis and efficacy, and, as here, defining new targets for parallel approaches.
The Council's initiative is likely to have salutary effects on: (1) persistent major illness or disability in our patients (2) the critical gap in scientific and mechanistic understanding of the clinical behaviour of the disease (3) companies and regulatory authorities who need tools to meet the expectation of regulatory authorities for commensurate long-term efficacy and safety, and thereby generate a competitive need for their organizations to show commitment to deeper clinical research (4) biopharmaceutical research plans after licensing where the presence of five licensed (four approved) therapies in Western Europe is inimical to the conduct of naïve blinded and controlled clinical trials and (5) because the mission of the consortium project engenders an unconventional multi-disciplinary and collaborative approach which should stimulate therapeutic discovery and technical spin-off development, for example, in assay kits for newly discovered prognostic biomarkers.
The consortium includes many of the key practitioners in the treatment of Gaucher disease and this project is very much about directly improving the quality of the care they provide. The proposed project aims to improve therapeutic outcomes and targeting, develop better trials, and introduce new prognostic diagnostics and, where possible, innovative therapies.
Outside the consortium, the clinical scientists from both the commercial academic sectors in this field use the academic literature as a key route by which they their own patient care, making academic publication is a key mechanism by which the impact of this research will be delivered. This will be supplemented by the engagement with patient groups and international societies in the field.
Close engagement with the companies who have joined the consortium means that there is a direct link to the providers of medicines to Gaucher patients. Through the open exchange of knowledge across the consortium, these companies can use to the research to develop new therapies and predictive methods based on improved understanding of the disease population.
Publications
Pavlova EV
(2019)
The lysosomal disease caused by mutant VPS33A.
in Human molecular genetics
Pavlova EV
(2015)
Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy.
in The Journal of pathology
Pavlova E
(2019)
The lysosomal disease caused by mutant VPS33A
Mullin S
(2019)
Evolution and clustering of prodromal parkinsonian features in GBA1 carriers.
in Movement disorders : official journal of the Movement Disorder Society
Massaro G
(2020)
Systemic AAV9 gene therapy using the synapsin I promoter rescues a mouse model of neuronopathic Gaucher disease but with limited cross-correction potential to astrocytes.
in Human molecular genetics
Marques AR
(2016)
Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular ß-glucosidases.
in Journal of lipid research
Klein A
(2016)
Identification of Modifier Genes in a Mouse Model of Gaucher Disease
in Cell Reports
Description | Chair of International Committe: Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe. |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | A European Advisory Council of experts in Gaucher disease describes the characteristics of eliglustat that are distinct from enzyme augmentation therapy (the standard of care) and miglustat (the other approved substrate reduction therapy) and recommends investigations and monitoring for patients on eliglustat therapy within the context of current recommendations for Gaucher disease management.Extensive metabolism of eliglustat by CYP2D6, and, to a lesser extent, CYP3A of the cytochrome P450 pathway, necessitates careful consideration of the patient's CYP2D6 metaboliser status and use of concomitant medications which share metabolism by these pathways. Guidance on specific assessments and monitoring required for eliglustat therapy, including an algorithm to determine eligibility for eliglustat, are provided. |
Description | Cochrane systematic Review in Gaucher disease |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | This document, of which I am senior author, summarizes all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease.It points to the apparent inadequacies resulting from trials in ultra-orphan diseases, despite transforming clinical effects and widespread use, acceptance and approval for marketing authorization of high-cost therapies internationally. The reviews probably did influence later consideration of trial designs and regulatory behaviour in the field - with subsequent adoption of astonishingly challenging randomized double-blinded controlled study data for clinical phase 3 trials of eliglustat leading to approval of Cerdelga in 2014 (FDA) and 2015 (EMA). A further update including the comprehensive phase 2 and phase 3 clinical trial programmes of eliglustat over 12 years in to be added in 2018. |
Description | Humanitarian Aid for patients with life-threatening Gaucher disease |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Provision of life-saving treatment free-of-charge by biopharmaceutical companies speaks for itself |
Description | NICE approval of Cerdelga for NHS England |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | I attended two NICE appraisals for an innovative oral therapy developed for Gaucher disease (eliglustat, now approved as Cerdelga after 14 years of clinical development in which I was chief investigator for one of the major phase 3 clinical trials). After rejection, this was approved finally for reimbursement in May 2017 and available for prescription in the NHS from September 2017. |
URL | https://www.nice.org.uk/guidance/hst5 |
Description | Biomedical Research Centre |
Amount | £114,300,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 04/2017 |
End | 03/2022 |
Description | GAUCHERITE |
Amount | £60,915 (GBP) |
Organisation | Medical Research Council (MRC) |
Department | MRC Stratified Medicine |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2013 |
End | 10/2017 |
Description | Investigator Initiated Research Grants Program Manager for Genetic Diseases |
Amount | £66,300 (GBP) |
Funding ID | IIR-GBR-001398 |
Organisation | Shire Pharmaceuticals |
Department | Shire UK |
Sector | Private |
Country | United Kingdom |
Start | 06/2017 |
End | 05/2018 |
Title | Authentic model myeloma and B-cell lymphoma |
Description | We have identified a unique model of non-Hodgkin B-Cell lymphoma/myeloma in mice with inducible Gaucher disease. This malignancy occurs with a high frequency in patients with Gaucher disease but the cause is unknown of this now-frequent cause of death. We have moreover shown that an approved drug, Eliglustat, completely prevents this complication - thus provoking a series of cause-and-effect experiments to understand the molecular pathogenesis of this important cancer - the second most common haematopoietic malignancy in humans. A patent of use has been filed. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Provided To Others? | No |
Impact | This tool will now serve an important role in studies of cancer causation and of the sequelae of Gaucher disease, an important sphingolipidosis. It, moreover, should allow better understanding of the development of these tumours and underscores the long-term use of Eliglustat as a high-affinity inhibitor of glycosphingolipid biosynthesis in patients with Gaucher disease. |
Title | Gaucherite database |
Description | This is a unique bespoke and relational database set up for the entire national specialist clinical centre network of investigators. It is a platform that is owned wholly by University of Cambridge and contains anonymised clinical data and investigative information, prospective and retrospective, from the cohort of British patients suffering from type I or III Gaucher disease. |
Type Of Material | Database/Collection of data |
Provided To Others? | No |
Impact | This enables a comprehensive conduct of the Gaucherite study in a secure platform to provide critical material for future stratified medicine projects and therapeutic research. |
URL | https://gaucherite.medschl.cam.ac.uk/ |
Description | Centre of Excellence award into Gaucher disease |
Organisation | Sanofi |
Country | Global |
Sector | Private |
PI Contribution | (1) Clinical experience, scientific expertise and pioneering of substrate -reduction strategy in Gaucher disease and other sphingolipidoses ( Tay-Sachs and Sandhoff disease; Niemann-Pick disease type C). (2) Unique genetically modified animal models of Gaucher disease with genetically determined comorbidities as observed in human patients (B-cell cancers and liver cancers). (3) Access to clinical samples ultimately DNA sequencing as well as international genetic collaboration into the understanding of genetic modifiers of neuronopathic variants of Gaucher disease in patients from collaborators in all from 12 countries. (4) Sub-contracted collaboration with Prof Sir John Hardy in the at the Dementia research Institute, UCL Institute of Neurology. |
Collaborator Contribution | Direct Scientific support and Indirect support including to the University research activities and analytical support for sophisticated sphingolipid quantification for experimental studies Provision of experimental diet and matched control diet for 12 month exposure in 3 distinct strains of experimental genetically modified mice with inducible Gaucher disease Two-way scientific discussions to be shared after 6 hours allocated presentation sessions (planned scientific visits cancelled because of Covid 2020-2022- deferred to 18 April 2023) related to sphingolipid-induced autoimmunity in Gaucher disease, experimental but postulated to account for severe hepatic disease in human subjects. These contributions are ongoing and not yet completed |
Impact | Confidential abstract presented at Gordon Research Conference in Sphingolipids and Glycobiology (27-31 March 2022) Publications in preparation |
Start Year | 2019 |
Description | Identification of Genetic modifiers in Krabbe disease |
Organisation | University of Oxford |
Department | Faculty of Music |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Neurodegenerative disease is becoming an increasing burden on healthcare and there is a continuing need to understand the cellular mechanisms involved and generate new therapeutic approaches. One important question to address is why distinct populations of neurons are vulnerable in these disorders despite widespread expression of the proteins involved. In recent years there has been a particular focus on the role of reactive oxygen species as factors that mediate the differential susceptibility of neurons. Indeed, oxidative stress and mitochondrial dysfunction have been implicated in all major neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Parkinson's and Alzheimer's disease. Furthermore, several pathogenic mutations in proteins that feature prominently in antioxidant pathways have been described in these disorders. Therefore, identification of pathways that counteract comparable injury and damage may identify new therapeutic strategies that are widely applicable to human disease. |
Collaborator Contribution | Professor Peter L Oliver and his team will provide molecular and sequencing data, as well as key strains for breeding, that will facilitate definitive identification of an important segregating locus or loci that determine severity and modify the expression of the underlying lysosomal Galc deficiency. He has access to mouse libraries and comprehensive collections that will facilitate the gene hunting. |
Impact | Setting up of key informative mouse breeding crosses for gene identification and tissue-focussed expression data. We have an internal collaboration in Neurosciences and a PhD student working on this subject to identify the neuro-inflammatory outcome. We have had poster presentations at the 2017 GRC and ESGLD meetings that in effect the strong background effects on disease expression are due to one or an integral number of modifier genetic effects. Genomics, genetics and neuropathological studies leave leeway for inspired collaborations. Ultimately, we will fully characterize the background strains and advance steadily to identify causal loci in implicated cDNA developmental gene cluster events. |
Start Year | 2017 |
Description | Principal Investigator on a Clinical trial of Venglustat - a brain-penetrant inhibitor of glucosylceramide biosynthesis in neuronopathic Gaucher disease |
Organisation | Sanofi |
Country | Global |
Sector | Private |
PI Contribution | We were the first group to test a unique brain-penetrant inhibitor of galacto-series glycosphingolipids in a genetically modified murine model of a neurodegenerative disease resembling acute neuronopathic Gaucher disease and Krabbe disease in the twitcher mouse. A succesful indication of target engagement and partial amelioration of psychosine mediated neuroinflammation as well as dosing information is highly relevant to human glycosphingolipidoses that affect the brain and nervous tissue would have strong implications for applicatiion to related dieases such as metachromatic leukodystrophy. |
Collaborator Contribution | Provision of the drug and sphingolipid analyses. |
Impact | Output published in 2022 Biomedicine and Pharmacotherapeutics |
Start Year | 2016 |
Title | Methods of Cancer Therapy |
Description | A glycosphingolipid biosynthesis inhibitor prevents lymphoproliferation and B-cell lymphoid malignancy in an authentic model of Type I Gaucher disease in mice. |
IP Reference | |
Protection | Copyrighted (e.g. software) |
Year Protection Granted | 2013 |
Licensed | Commercial In Confidence |
Impact | This will underpin the clinical use of Eliglustat. |
Title | Clinical trial of Eliglustat - four year results of phase 3 study |
Description | Four year follow-up data on phase 3 trial of Gaucher disease therapy with novel agent eliglustat |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Wide-scale adoption |
Year Development Stage Completed | 2016 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | This is a novel therapy. The pase 3 trial led to authorization. The four year data show continuing safety and efficacy |
URL | https://www.sanofigenzyme.com/en/products-research/research-pipeline;https://news.genzyme.com/press-... |
Title | Substrate Reduction therapy |
Description | Substrate reduction therapy with a unique biosynthetic inhibitor of glycosphinglipid formation able to penetrate the CNS and orally active. Here applied in the Amethist trial with venglustat for late-onset and juvenile GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) as well as GM1 glangliosidosis Builds on earlier trial proof-of-principle of miglustat in type 1 Gaucher disease published Lancet 2000 - approved worldwide for Gaucher disease in 2003 and for Niemann-Pick diseasse type C in 2007). Novel class venglutat also being explored in LEAP Study in neuronpathic Gaucher disease. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2020 |
Development Status | Under active development/distribution |
Impact | LEAP trial Safety and early efficacy in neuronopathic Gaucher disease demonstrated. Two year data emerging and being submitted for publication in full. I am PI in trial and encouraged application to cognate diseases such a late-onet GM2 gangliosidosis - Tay-sachs and Sandhoff disease principally. This is happening Amethist trial (I m a PI) |
URL | https://clinicaltrials.gov/ct2/show/NCT02843035 |
Description | Advanced course on diagnosis and treatment of metabolic diseases and Clinical Approach to the Diagnosis of Lysosomal Diseases |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The teaching inspired other professionals and fully engaged students Professor Cox also met with healthcare professionals in the hospital in Porto Alegre to discuss patients suffering from Gaucher disease |
Year(s) Of Engagement Activity | 2014 |
Description | Benoziyo Lecture (The Weizmann Institute) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The lecture sparked much interest Professor Cox's lecture was greatly appreciated and much enjoyed by all |
Year(s) Of Engagement Activity | 2012 |
Description | European Calcified Tissue Society (ECTS) Congress, Prague |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Professor Cox's presentation sparked enthusiasm and questions for discussion Awareness of certain aspects of his talk was heightened |
Year(s) Of Engagement Activity | 2014 |
Description | Gaucher Bone meeting in Seoul, South Korea |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The presentation was well received and invoked questions and discussion Following the talk awareness of Gaucher disease was heightened and awareness of certain aspects of the disease were increased |
Year(s) Of Engagement Activity | 2014 |
Description | Gaucher Leadership Forum in Madrid in November 2013 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Professor Cox's talk sparked questions and attracted huge interest Professor Cox has been asked to give a presentation at the Gaucher Leadership Forum in Berlin in 2015 |
Year(s) Of Engagement Activity | 2013 |
Description | Gordon research conference - lysosomal diseases |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | GRS - The purpose was educational engagement for basic and clinical scientists in lysosomal diseases: Decoding Lysosomal Signals to Understand Disease Mechanisms and Define New Therapeutic Strategies for Lysosomal Storage Disorders. This Gordon Research Seminar attracted 50 participants - all slots filled. I delivered the opening keynote lecture. At the subsequent 2017 GRC (Gordon Research Conference) ); a paper on upcoming new data was presented from our institution describing a unique new disease due to human mutations in the endosomal-lysosomal related protein of the HOPS complex, VPS 33A. A research poster by my senior colleague describing strong modifier effects related to genetic background in a severe neurological disease in mice (twitcher 2J and twitcher 5J) that accurately model human Krabbe disease. I delivered an opening translational lecture on therapeutics in sphingolipidoses and chaired a half-day session on lysosomal therapeutics. al our contributions appeared to be well received. Finally I was a discussion leader in a half-day session dedicated to therapeutic advances in this field. Later I was proposed and after a majority democratic vote, elected Vice-Chair to be followed by Chair of the GRCs in 2019 and 2021. I also delivered a keynote lecture at the 2016 Zing conference in Cambridge on Lysosomal diseases to a mixed professional and biochemical audience. |
Year(s) Of Engagement Activity | 2011,2013,2015,2017 |
URL | https://www.grc.org/home.aspx |
Description | International Neuronopathic Gaucher disease consortium |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | This is an international research collaboration spun out of the UK Gaucherite programme and cohort funded intellectually free by a commercial collaborative award to identify modfier genes that determine the phenotype of neuronpathic Gaucher disease. Investigators from 13 countries are engaged; patients from 12 countires across the word. Clinical protocols collected and gDNA whole exome sequencing outcome now available form about 420 nGD patients. Bioinformatic analysis to address central questions shortly to start. |
Year(s) Of Engagement Activity | 2014,2015,2016,2017,2018,2019,2020,2021,2022,2023 |
Description | Macedonian Academy of Sciences and Arts |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The presentation will spark interest and discussion A heightened awareness of various aspects of Gaucher disease |
Year(s) Of Engagement Activity | 2014 |
Description | Marie-Curie sphingonet summer school workshop, University of Oxford |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | The presentation sparked interest and discussion Some students were keen to take their scientific studies further |
Year(s) Of Engagement Activity | 2013 |
Description | Un Conte de deux Cites (Cle du Lysosome Award) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Professor Cox's talk sparked huge interest and admiration for his research work into lysosomal disorders Much awareness was raised into lysosomal disorders |
Year(s) Of Engagement Activity | 2013 |
Description | University of Cambridge Department of Medicine Research Day |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | The talk sparked questions and raised awareness New insights into Gaucher disease were shared |
Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014 |
Description | Zimmern Lecture in Medicine |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | The lecture sparked great interest and raised many questions After the talk, great interest was shown in my research activities |
Year(s) Of Engagement Activity | 2009 |