Engineering human artificial chromosomes containing the dystrophin locus for autologous cell therapy of Duchenne Muscular Dystrophy.
Lead Research Organisation:
University College London
Department Name: Cell and Developmental Biology
Abstract
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy (1/3500 males). It affects skeletal and cardiac muscles, leading to progressive loss of movements, confinement to a wheelchair and finally to total paralysis and assisted ventilation. Death occurs usually in the third decade of life because of cardiac and/or respiratory failure. Improved medical assistance has increased the lifespan of patients but still there is no efficacious therapy and steroids are the only palliative treatment available. Among several novel strategies that are entering clinical experimentation, our group focused on cell therapy, based upon intra-arterial infusion of mesoangioblasts (MABs), stem/progenitor cells associated to blood vessels that showed efficacy in dystrophic mice and dogs. Although a phase I/II clinical trial based upon allogeneic transplantation of mesoangioblasts is currently running, gene therapy of autologous cells would be preferable (no immune suppression and no need of HLA-matched donor) but the large size of the dystrophin gene (2.4Mb) hampers the use of viral vectors. Our group pioneered the use of human artificial chromosomes (HACs) containing the whole dystrophin locus for muscular dystrophy (DYS-HAC), showing efficacy of this strategy in dystrophic mouse cells. Based on the above, we now plan to develop a definitive strategy that would allow translation to human cells and boosting the therapeutic effect.
First, we will insert into the DYS-HAC an "immortalizing cassette" containing genes that allow bypassing senescence (telomerase and Bm1) and a suicide gene as a safety device. Preliminary results confirm that this cassette works in human cells. The cassette is floxed and thus can be excised from the HAC before cells are infused into patients.The DYS-HAC will also contain an inducible MyoD (i.e linked to the Estrogen Receptor: MyoD-ER), a myogenic master gene that will allow induction of muscle differentiation (which is variable among different patients).
The optimal number of copies of dystrophin to include will be determined to achieve the optimal level of expression for a single genetically corrected nucleus to compensate for the muscle fibre resident nuclei that cannot synthesize it. All the subsequent generations of HACs will be transferred in human dystrophic mesoangioblasts that will be then challenged for their ability to repair dystrophic muscle and ameliorate the disease.
The PI is a leader in the field of cell therapy; his expertise, and that of his colleagues, will guarantee a high probability of success for this ambitious but realistic project, whose results may lead to rapid clinical translation and, at the same time, pave the way for other monogenic diseases, characterized by mutations of a very large gene.
First, we will insert into the DYS-HAC an "immortalizing cassette" containing genes that allow bypassing senescence (telomerase and Bm1) and a suicide gene as a safety device. Preliminary results confirm that this cassette works in human cells. The cassette is floxed and thus can be excised from the HAC before cells are infused into patients.The DYS-HAC will also contain an inducible MyoD (i.e linked to the Estrogen Receptor: MyoD-ER), a myogenic master gene that will allow induction of muscle differentiation (which is variable among different patients).
The optimal number of copies of dystrophin to include will be determined to achieve the optimal level of expression for a single genetically corrected nucleus to compensate for the muscle fibre resident nuclei that cannot synthesize it. All the subsequent generations of HACs will be transferred in human dystrophic mesoangioblasts that will be then challenged for their ability to repair dystrophic muscle and ameliorate the disease.
The PI is a leader in the field of cell therapy; his expertise, and that of his colleagues, will guarantee a high probability of success for this ambitious but realistic project, whose results may lead to rapid clinical translation and, at the same time, pave the way for other monogenic diseases, characterized by mutations of a very large gene.
Technical Summary
The aim of this project is to develop a novel cell therapy for Duchenne Muscular Dystrophy (DMD) based upon transplantation of autologous mesoangioblasts (MABs; vessel associated progenitors) engineered with a human artificial chromosome (HAC) vector containing the entire 2.4 megabases of the human dystrophin locus (DYS-HAC). Specifically we will insert into the DYS-HAC:
a) Floxed immortalizing sequences (human telomerase reverse transcriptase (hTERT), Bmi-1 and the suicide gene Herpex Simplex Virus Thymidine Kinase (HSV-TK). These will allow us to extend, reversibly, the lifespan of primary human MABs, excision of the floxed cassette by a non-integrating lentiviral vector expressing the Cre recombinase and negative selection of cells where the cassette has not been excised;
b) An inducible MyoD (MyoD-ER) where the myogenic factor is linked to the Estrogen Receptor, to induce myogenesis at will, since mesoangioblasts vary in their myogenic potency among different patients.
c) Two or more full-length human dystrophin cDNAs to compensate for gene dosage insufficiency deriving from fusion of relatively few genetically corrected cells in a fiber containing a large majority of genetically defective nuclei. Transfer of different HACs, each with a different selection marker, will allow us to determine the number of copies required for optimal protein production.
Subsequent generations of HACs, progressively incorporating the above mentioned functions, will be built and transferred into MABs from DMD patients. Proliferation, differentiation, transformation/tumorigenicity of cells will be tested in vitro and in vivo (scid/mdx dystrophic and immune-deficient mice) before and after excision of floxed immortalizing sequences (by a non-integrating lentiviral vector). Engraftment, dystrophin production, amelioration of the pathology and functional recovery will be tested in transplanted mice. This project will set the stage for a definitive cell therapy of DMD.
a) Floxed immortalizing sequences (human telomerase reverse transcriptase (hTERT), Bmi-1 and the suicide gene Herpex Simplex Virus Thymidine Kinase (HSV-TK). These will allow us to extend, reversibly, the lifespan of primary human MABs, excision of the floxed cassette by a non-integrating lentiviral vector expressing the Cre recombinase and negative selection of cells where the cassette has not been excised;
b) An inducible MyoD (MyoD-ER) where the myogenic factor is linked to the Estrogen Receptor, to induce myogenesis at will, since mesoangioblasts vary in their myogenic potency among different patients.
c) Two or more full-length human dystrophin cDNAs to compensate for gene dosage insufficiency deriving from fusion of relatively few genetically corrected cells in a fiber containing a large majority of genetically defective nuclei. Transfer of different HACs, each with a different selection marker, will allow us to determine the number of copies required for optimal protein production.
Subsequent generations of HACs, progressively incorporating the above mentioned functions, will be built and transferred into MABs from DMD patients. Proliferation, differentiation, transformation/tumorigenicity of cells will be tested in vitro and in vivo (scid/mdx dystrophic and immune-deficient mice) before and after excision of floxed immortalizing sequences (by a non-integrating lentiviral vector). Engraftment, dystrophin production, amelioration of the pathology and functional recovery will be tested in transplanted mice. This project will set the stage for a definitive cell therapy of DMD.
Planned Impact
Although cardiovascular and neurological diseases remain the most widespread and disabling in the Western world, musculoskeletal impairments are among the most frequent causes of disability, encompassing more than 150 diseases and affecting every age and socioeconomic group. The classic example is muscular dystrophy, which can appear from infancy to adulthood and affects over 300,000 European citizens. This group of diseases alone poses serious social and economic problems for each national health system, considering the cost for repeated hospitalizations, home assistance, physiotherapy, surgery, medical devices for a devastating disease that takes now decades from diagnosis to death with a progressively deterioration of life quality.
Our project aims to demonstrate safety and efficacy for rapid clinical translation of this cell therapy strategy for Duchenne muscular dystrophy, though restricted to patients in a paediatric age and whose mutation cannot be treated by the simpler exon-skipping strategy. We aim to achieve a significant stabilization/amelioration of clinical symptoms. Importantly, even a partial effect would produce an enormous benefit for patients.
Together with patients, their families would benefit of the success of this project, not only in terms of emotional impact but also in practical terms, due to a reduction of the daily heavy burden related to continuous assistance to patients who are non ambulant and, later, totally unable to move.
The National Health Service would also indirectly benefit, not only for the implementation of available therapies, but also in economic terms. Although cell therapies are expensive and patient-tailored, they would still be cheaper that the total costs for the NHS, related to diagnosis, medical care, surgery, physiotherapy, drugs, medical devices that are required for decades.
Our project aims to demonstrate safety and efficacy for rapid clinical translation of this cell therapy strategy for Duchenne muscular dystrophy, though restricted to patients in a paediatric age and whose mutation cannot be treated by the simpler exon-skipping strategy. We aim to achieve a significant stabilization/amelioration of clinical symptoms. Importantly, even a partial effect would produce an enormous benefit for patients.
Together with patients, their families would benefit of the success of this project, not only in terms of emotional impact but also in practical terms, due to a reduction of the daily heavy burden related to continuous assistance to patients who are non ambulant and, later, totally unable to move.
The National Health Service would also indirectly benefit, not only for the implementation of available therapies, but also in economic terms. Although cell therapies are expensive and patient-tailored, they would still be cheaper that the total costs for the NHS, related to diagnosis, medical care, surgery, physiotherapy, drugs, medical devices that are required for decades.
Organisations
- University College London (Lead Research Organisation)
- University of Manchester (Collaboration)
- University College London (Collaboration)
- Leiden University (Collaboration)
- Sapienza University of Rome (Collaboration)
- European Federation of Pharmaceutical Industries and Associations (EFPIA) (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- Stem Cell Technologies (Collaboration)
- Swiss Federal Institute of Technology in Lausanne (EPFL) (Collaboration)
- University of Strasbourg (Collaboration)
- University of Sheffield (Collaboration)
- Pompeu Fabra University (Collaboration)
- University of Dresden (Collaboration)
- Pluriomics BV (Collaboration)
- European Commission (Collaboration)
Publications
Benedetti S
(2013)
Repair or replace? Exploiting novel gene and cell therapy strategies for muscular dystrophies.
in The FEBS journal
Benedetti S
(2018)
Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.
in EMBO molecular medicine
Benedetti S
(2015)
Reversible immortalization allows human artificial chromosome-mediated gene correction of human dystrophic muscle progenitor cells
in Neuromuscular Disorders
Benedetti S
(2015)
Gene and Cell Therapy: Therapeutic Mechanisms and Strategies
Benedetti S.
(2015)
Human artificial chromosome-mediated genetic correction of human dystrophic skeletal muscle progenitors for the autologous cell therapy of Duchenne muscular dystrophy
in HUMAN GENE THERAPY
Benedetti Sara
(2018)
Next-Generation Human Artificial Chromosomes for Autologous Cell Therapy of Duchenne Muscular Dystrophy
in MOLECULAR THERAPY
Bonfanti C
(2015)
PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
in Nature communications
Camps J
(2020)
Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles.
in Cell reports
Title | La trama della vita (The frame of life). Marsilio editor. |
Description | Living forever is a long-lasting dream, present in many novels, paintings and musical pieces. Who knows whether this dream may one day come true? Regenerative medicine, the topic of the book, promises not only to cure terrible and so far incurable diseases, but also to repair or replace our cells and tissues so that, in theory, we may live "forever young and healthy". Do we really want this? Moreover, for few spectacular successes, there have been many more failures. Nevertheless, the expectations raised in patients have been exploited by commercially driven "stem cell clinics" that offer to cure any disease with stem cells in exchange for much money. These and other topics such as the impact on society and health economics are discussed in this book. |
Type Of Art | Creative Writing |
Year Produced | 2018 |
Impact | The book, currently in Italian, explains to a lay audience promises and problems of regenerative medicine and its impact on society. The book was sold out and is currently a finalist for the Galieo prize for scientific outreach. |
Description | Co-organiser, Myopathology Symposium |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://www.bns.org.uk/event/3052-2/ |
Description | Course co-organiser: UCL CELL0012 Stem Cells and Regenerative Medicine |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Co-organiser of one of UCL's most successful stem cell courses (60 enrolled). |
URL | https://www.ucl.ac.uk/lifesciences-faculty-php/courses/viewcourse.php?coursecode=CELL0012 |
Description | Faculty, EUREKA Summerschool on Translational Medicine, Utrecht (NL), Jul 2018 |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Faculty, EUREKA Summerschool on Translational Medicine, Utrecht (NL), Jul 2018 |
URL | https://eurekainstitute.org/utrecht-summerschool-course-2017-2/ |
Description | Presentation to general paediatricians |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Two seminars were given in UK hospitals, including a district general hospital. Target audience: secondary care paediatricians. Positive feedback were given following this event, as clinicians felt they knew much more on the new therapeutic options for muscular dystrophy. |
Description | Teaching session for clinicians on new therapies for muscular dystrophies |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Teaching session for clinicians on new therapies for muscular dystrophies (North Middlesex Hospital, London, UK: paediatric department) |
Description | UCL Co-lead, London Stem Cell Network |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Established of the first London-wide stem cell network, with first symposium oversubscribed and highly successful. |
URL | https://lscn.crick.ac.uk |
Description | UK Academic Foundation Programme Interview Panel, London, 2019 |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Interview panel member of the prestigious UK Academic Foundation Programme. The Academic Foundation Programme is a clinical specialty training providing an opportunity for foundation doctors to develop research, teaching and leadership/management skills in addition to the clinical competences outlined in the Foundation Programme Curriculum. |
URL | https://foundationprogramme.nhs.uk/programmes/2-year-foundation-programme/academic-training/ |
Description | A universal donor mesoangioblast for the therapy of muscular dystrophy and other recessive genetic diseases of the mesoderm. |
Amount | £178,000 (GBP) |
Funding ID | 20150256 |
Organisation | University of Manchester |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2019 |
End | 03/2020 |
Description | Collaborative research grant |
Amount | € 398,826 (EUR) |
Funding ID | 201440.30.31.32 |
Organisation | La Marató de TV3 Foundation |
Sector | Charity/Non Profit |
Country | Spain |
Start | 06/2015 |
End | 06/2018 |
Description | ERC Starting Grant "HISTOID" |
Amount | € 1,500,000 (EUR) |
Funding ID | 759108 |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 08/2018 |
End | 08/2023 |
Description | Editing the Nuclear Envelope: Using Human Induced Pluripotent Stem Cells and CRISPR-Cas Technology to Develop Novel Therapies for Skeletal Muscle Laminopathies |
Amount | £114,556 (GBP) |
Funding ID | 19GRO-PS48-0188 |
Organisation | Muscular Dystrophy UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2019 |
End | 09/2023 |
Description | European Research Council Starting Grant |
Amount | € 1,499,738 (EUR) |
Funding ID | HISTOID |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 05/2018 |
End | 05/2023 |
Description | Immortal, universal donor cells for the ex vivo gene therapy of muscular dystrophy: development of a pre-clinical mouse model. |
Amount | £61,937 (GBP) |
Funding ID | MR/S015116/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2019 |
End | 05/2020 |
Description | In vivo modelling of Duchenne muscular dystrophy using patient-specific iPS cell-derived artificial muscles for therapy development" |
Amount | € 25,000 (EUR) |
Organisation | Duchenne Parent Project Holland |
Sector | Charity/Non Profit |
Country | Netherlands |
Start | 08/2019 |
End | 08/2020 |
Description | London Interdisciplinary Doctoral Programme |
Amount | £21,793,243 (GBP) |
Funding ID | BB/M009513/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2015 |
End | 09/2024 |
Description | Muscular Dystrophy Campaign PhD Studentship |
Amount | £114,326 (GBP) |
Funding ID | RA4/3023/1 |
Organisation | Muscular Dystrophy UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2018 |
Description | New Frontier Science |
Amount | $364,623 (USD) |
Organisation | Takeda Pharmaceutical Company |
Sector | Private |
Country | Japan |
Start | 02/2014 |
End | 07/2016 |
Description | PhD Studenship |
Amount | £77,314 (GBP) |
Funding ID | BB/J014567/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2014 |
End | 09/2017 |
Description | PluriMes EC FP7 consortium |
Amount | € 6,000,000 (EUR) |
Funding ID | 602423 |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Sector | Public |
Country | European Union (EU) |
Start | 02/2014 |
End | 01/2018 |
Description | Research Grant |
Amount | £46,000 (GBP) |
Organisation | Duchenne Parent Project Onlus Italy |
Sector | Charity/Non Profit |
Country | Italy |
Start | 07/2015 |
End | 02/2017 |
Description | Understanding motor neuron and muscle disease using human stem cells |
Amount | £73,500 (GBP) |
Funding ID | Main PI: Dr Rickie Patani (Co-I: Dr Tedesco) |
Organisation | Rosetrees Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2018 |
End | 09/2021 |
Title | A Highly Efficient Method of Microcell Production for Chromosome Transfer |
Description | Microcell-mediated chromosome transfer (MMCT) is a method that enables the transfer of chromosomes from donor to recipient cells. It involves fusion of microcells (small particles of nuclear and plasma membrane containing one or a few chromosomes) with cells, and the following selection of cell hybrids. MMCT can be used to study in-vitro, or in-vivo outcomes of the transferred chromosome with a range of cell lines. We have developed a method to overcome current obstacles that are limiting MMCT utilisation. This protocol results in a cost-effective microcell manufacturing procedure that is amenable to scale-up and diffuse microcell-based technologies such as HAC-transfer for gene therapy. |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | We obtained a decrease in cost and time complemented by a significant increase in the number of microcells extracted, eliminating the requirement of a super-centrifuge machine, setting the basis to scale-up microcell production for chromosome transfer. |
Title | A new HAC containing an inducible MyoD (MyoD-ER) |
Description | A tamoxifen inducible MyoD was inserted inside the new HAC in order to induce muscle differentiation upon tamoxifen administration. |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | It is expected that this reagent will facilitate muscle differentiation of cells harboring the novel HAC |
Title | A novel DYS-HAC, devoid of immunogenic proteins (e-GFP and HSTK) with floxed resistance genes |
Description | A new intermediate HAC has been developed after removal of HSTK and GFP that are strongly immunogenic. In addition, resistance genes (also potentially immunogenic but needed for selection) have been floxed so that they can be excised when needed |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | The new vectors will be instrumental towards the building of the final HAC, aim of this project. |
Title | A novel method for direct microcell production for HAC transfer from DT40 cells |
Description | We have developed a new method that allows adhesion of chicken DT40 cells (normally growing in suspension) for direct production of microcells. |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | Microcells could be then directly used to target cells for HAC transfer. This method significantly accelerate HAC transfer, avoiding the intermediate step of transfer into Chinese Hamster Ovary cells. |
Title | Construction of a new Dys-HAC-13 |
Description | We have developed a new Dys-HAC, named 13, containing a inducible Caspase9, followed by an inducible human MyoD-ER and codon-optimised human dystrophin cDNA, driven by SPC5-12 (a synthetic potent muscle specific promoter), and multi integrate and mutated p-lox sites. |
Type Of Material | Cell line |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | This new construct will allow the derived human cell line, to undergo robust muscle differentiation at our will (MyoD-ER), to be susceptible to induced apoptosis (as a safety devise through i-Caspase 9) and to over produce dystropin. |
Title | Construction of a new Dys-HAC-14 and 15 |
Description | We have constructed a new Dys-HAC containing Blasticidin gene, EGFP and an immortalising cassette (Bmi-1, Telomerase and HSTK suicide gene) and finally an inducible Cre-ERT2 gene that may allow to remove this flexed cassette from the HAC upon Ganciclovir treatment. The two constructs (14 and 15) differ for the location and method of integration into the HAC. |
Type Of Material | Cell line |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | These novel constructs, ready to be transferred into human cells will allow the induction of unlimited proliferation (thanks to Bmi-1 and Telomerase) and at the same time, excision of the function when differentiation or transplantation will be required. Since Cre mediated excision is never 100% efficient we also have an inducible suicide gene (HSTK) which allows to selectively kill those cells (10% in preliminary experiments) where the cassette is not excised. Remarkably, human cells, with the same active cassette (though in a different molecular context) are not tumorigenic in immune deficient mice. |
Title | Human dystrophic (DMD) reversibly immortalized mesoangioblasts containing DYS-HAC2 |
Description | We have succeeded in obtaining 8 different clones of lentiviral reversibly immortalised mesoangioblasts from Duchenne patients containing a novel DYS-HAC (DYS-HAC2) with reduced immunogenic potential. |
Type Of Material | Cell line |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | This is the first evidence of HAC transfer in clinically relevant cell types. Transplantation studies showed engraftment in dystrophic mice and the same method is currently being applied to transfer DYS-HAC2 also to human myoblasts. |
Title | Novel DYS-HAC sequence (and human MyoD-ER plasmid) |
Description | We have almost completed the designing of the final sequence of a novel multifunctional DYS-HAC. This includes a number of genes regulating proliferation, differentiation and safety of the construct. Those genes are assembled into two large DNA vectors and we will be sending them very shortly for gene-synthesis. Afterwards we will modify our current HAC backbone by inserting those sequences by chromosome engineering. As a proof of principle for our approach, we have successfully synthesized and |
Type Of Material | Biological samples |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | The development of this material is critical for the successful development of the project since it constitutes one of the main parts to engineer the novel HAC. Notably, this will be the first evindece of gene-synthesis mediated chromosomal engineering. If successful this technique will significantly impact on the chromosomal engineering community providing a way to facilitate what is usually a time consuming and technically challenging process. |
Title | Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles |
Description | Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | 1) 1.5EUR million ERC Starting Grant 2) Promotion to Full Professor 3) Group Leader at Francis Crick Insitute |
URL | https://www.sciencedirect.com/science/article/pii/S2211124718304522?via%3Dihub |
Title | Two new DMD iPSC lines |
Description | Duchenne muscular dystrophy (DMD) is the most common paediatric muscular dystrophy and is caused by mutations in the DYSTROPHIN gene. We generated two induced pluripotent stem cell (iPSC) lines from DMD patients with nonsense mutations in exons 68 (UCLi011-A) or 70 (UCLi012-A) by transfecting reprogramming mRNAs. Both mutations affect expression of all dystrophin isoforms. iPSCs expressed pluripotency-associated markers, differentiated into cells of the three germ layers in vitro and had normal karyotypes. The selected mutations are potentially amenable to read-through therapies, exon-skipping and gene-editing. These new iPSCs are also relevant to study DYSTROPHIN role in tissues other than skeletal muscle. |
Type Of Material | Cell line |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Contacted by a company in the Netherlands to provide them these cell lines |
URL | https://www.sciencedirect.com/science/article/pii/S1873506119303186?via%3Dihub |
Title | Model to assess gene and cell therapies on human artificial muscles |
Description | We have developed two methods to assess gene and cell therapies efficacy on human bioengineered muscles which have the potential to dramatically reduce dependence on animal models to do so. |
Type Of Material | Data analysis technique |
Year Produced | 2022 |
Provided To Others? | No |
Impact | Internally in our research group this has already reduced to almost zero the reliance on animal models to assess gene and cell therapy vectors. Two papers describing these methods are currently under revision in major scientific journals. |
URL | https://doi.org/10.21203/rs.3.pex-2034/v1 |
Title | RNAseq of muscle stem cells |
Description | RNAseq of mouse, human primary and iPSC-derived myogenic progenitors treated with DLL4 and PDGFBB to enhance migration |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Preprint manuscript deposited and RNAseq reads to be made available upon acceptance of the manuscript for full publication |
URL | https://www.biorxiv.org/content/10.1101/2021.02.28.431778v1 |
Description | EBiSC Consortium |
Organisation | European Commission |
Department | Innovative Medicines Initiative (IMI) |
Country | Belgium |
Sector | Public |
PI Contribution | The role of my team is to generate cell lines and tool to study muscle diseases and develop therapies. Specific role: • WP 2.1 - Standardisation of protocols for recruitment of tissue and clinical data - Commissioned iPSC production • WP 6.2 Selection of disease types for the PoC trials - PoC differentiation - Scalable production of specific progenitor cells (FM & FST) |
Collaborator Contribution | From EBISC website: "The EBiSC Consortium represents all relevant stakeholders from tissue donors to clinical and academic iPSC researchers and industrial users and thus provides the scientific expertise, facilities, networks and experience to achieve the project goals and respond appropriately to advances in science and society. Led by Pfizer Ltd and managed by Roslin Cells Sciences Ltd., the Consortium comprises 8 active participant iPSC Centres with clinical and patient networks, a global leader in industrial iPSC supply, international experts in iPSC science, biobanking, bioengineering, regenerative medicine and data management, and scholars in law and ethics." Full list of partners below. EFPIA companies: - Pfizer Ltd, United Kingdom - Novo Nordisk A/S, Denmark - AstraZeneca AB, Sweden - H. Lundbeck A/S, Denmark - Janssen Pharmaceutica NV a pharmaceutical company of Johnson & Johnson, Belgium - UCB Biopharma SPRL, Belgium - Bayer Pharma AG, Germany - Eli Lilly & Co. Ltd, United Kingdom SME's: - Roslin Cell Sciences, United Kingdom - ARTTIC, France - DefiniGEN Ltd, United Kingdom - Douglas Connect GmbH (working communities), Switzerland - Bioneer A/S, Denmark Universities, research organisations, public bodies, non-profit groups - University of Edinburgh, United Kingdom - Fraunhofer-Institut für Biomedizinische Technik (IBMT), Germany - Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie IME ScreeningPort (IME-SP), Germany - Genome Research Limited (Wellcome Trust Sanger Institute), United Kingdom - European Molecular Biology Laboratory (European Bioinformatics Institute), United Kingdom - Charité Universitätsmedizin Berlin, Germany - University of Newcastle Upon Tyne, United Kingdom - Klinikum der Universität zu Köln (University of Cologne), Germany - Gottfried Wilhelm Leibniz Universität Hannover (University of Hannover) Centre for Ethics and Law in the Life Sciences, Germany - Koninklijke Nederlandse Academie van Wetenschappen (The Hubrecht Institute), Netherlands - University College London, United Kingdom - Culture Collections of Public Health England, United Kingdom - National Institute for Biological Standards and Control, United Kingdom - Universitätsklinikum Bonn (University of Bonn), Germany - Instituto de Salud Carlos III. (Spanish Stem Cell Bank), Spain - Fundacion Publica Andaluza Progreso y Salud, Spain - Center of Regenerative Medicine in Barcelona (CMR[B]), Spain - Inbiomed, Spain |
Impact | This collaboration is highly multi-disciplinary (please see list of collaborators above) and has already resulted in an agreement to deposit and bank two iPS cell lines from patients with rare muscle diseases. |
Start Year | 2016 |
Description | EBiSC Consortium |
Organisation | European Federation of Pharmaceutical Industries and Associations (EFPIA) |
Country | Belgium |
Sector | Private |
PI Contribution | The role of my team is to generate cell lines and tool to study muscle diseases and develop therapies. Specific role: • WP 2.1 - Standardisation of protocols for recruitment of tissue and clinical data - Commissioned iPSC production • WP 6.2 Selection of disease types for the PoC trials - PoC differentiation - Scalable production of specific progenitor cells (FM & FST) |
Collaborator Contribution | From EBISC website: "The EBiSC Consortium represents all relevant stakeholders from tissue donors to clinical and academic iPSC researchers and industrial users and thus provides the scientific expertise, facilities, networks and experience to achieve the project goals and respond appropriately to advances in science and society. Led by Pfizer Ltd and managed by Roslin Cells Sciences Ltd., the Consortium comprises 8 active participant iPSC Centres with clinical and patient networks, a global leader in industrial iPSC supply, international experts in iPSC science, biobanking, bioengineering, regenerative medicine and data management, and scholars in law and ethics." Full list of partners below. EFPIA companies: - Pfizer Ltd, United Kingdom - Novo Nordisk A/S, Denmark - AstraZeneca AB, Sweden - H. Lundbeck A/S, Denmark - Janssen Pharmaceutica NV a pharmaceutical company of Johnson & Johnson, Belgium - UCB Biopharma SPRL, Belgium - Bayer Pharma AG, Germany - Eli Lilly & Co. Ltd, United Kingdom SME's: - Roslin Cell Sciences, United Kingdom - ARTTIC, France - DefiniGEN Ltd, United Kingdom - Douglas Connect GmbH (working communities), Switzerland - Bioneer A/S, Denmark Universities, research organisations, public bodies, non-profit groups - University of Edinburgh, United Kingdom - Fraunhofer-Institut für Biomedizinische Technik (IBMT), Germany - Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie IME ScreeningPort (IME-SP), Germany - Genome Research Limited (Wellcome Trust Sanger Institute), United Kingdom - European Molecular Biology Laboratory (European Bioinformatics Institute), United Kingdom - Charité Universitätsmedizin Berlin, Germany - University of Newcastle Upon Tyne, United Kingdom - Klinikum der Universität zu Köln (University of Cologne), Germany - Gottfried Wilhelm Leibniz Universität Hannover (University of Hannover) Centre for Ethics and Law in the Life Sciences, Germany - Koninklijke Nederlandse Academie van Wetenschappen (The Hubrecht Institute), Netherlands - University College London, United Kingdom - Culture Collections of Public Health England, United Kingdom - National Institute for Biological Standards and Control, United Kingdom - Universitätsklinikum Bonn (University of Bonn), Germany - Instituto de Salud Carlos III. (Spanish Stem Cell Bank), Spain - Fundacion Publica Andaluza Progreso y Salud, Spain - Center of Regenerative Medicine in Barcelona (CMR[B]), Spain - Inbiomed, Spain |
Impact | This collaboration is highly multi-disciplinary (please see list of collaborators above) and has already resulted in an agreement to deposit and bank two iPS cell lines from patients with rare muscle diseases. |
Start Year | 2016 |
Description | HACs and iPS cells for DMD |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Generation of preliminary data to apply and secure further funding from the Muscular Dystrophy Campaign |
Collaborator Contribution | Professor Muntoni, a world leading paediatric neurologist, is the second supervisor of a PhD studentship secured by Dr Tedesco |
Impact | Muscular Dystrophy Campaign-funded 4-year PhD studentship grant to Dr Tedesco from Jan 2015 and NIHR ACF. Please see specific section for additional details. |
Start Year | 2013 |
Description | New stem cell therapy for Duchenne muscular dystrophy |
Organisation | Pompeu Fabra University |
Country | Spain |
Sector | Academic/University |
PI Contribution | My team focuses on studying the self-renewal capacity of transplantable muscle stem cells and the possibility to correct them with human artificial chromosomes. |
Collaborator Contribution | Dr Serrano (Pompeu Fabra University, Barcelona) is focusing on developing anti-fibrotic treatments that could be coupled with myogenic cell transplantation. Prof Cossu (Manchester University) is focusing on developing genetic treatments tat could be coupled with myogenic cell transplantation (via exon skipping). |
Impact | Publications (e.g. Tedesco FS et al., Methods in Molecular Bioogy. 2017;1556:129-147) and presentations at international conferences (e.g. FASEB conference "Skeletal Muscle Stem Cells and Regeneration", Keystone (CO), Jul 2016). |
Start Year | 2015 |
Description | New stem cell therapy for Duchenne muscular dystrophy |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My team focuses on studying the self-renewal capacity of transplantable muscle stem cells and the possibility to correct them with human artificial chromosomes. |
Collaborator Contribution | Dr Serrano (Pompeu Fabra University, Barcelona) is focusing on developing anti-fibrotic treatments that could be coupled with myogenic cell transplantation. Prof Cossu (Manchester University) is focusing on developing genetic treatments tat could be coupled with myogenic cell transplantation (via exon skipping). |
Impact | Publications (e.g. Tedesco FS et al., Methods in Molecular Bioogy. 2017;1556:129-147) and presentations at international conferences (e.g. FASEB conference "Skeletal Muscle Stem Cells and Regeneration", Keystone (CO), Jul 2016). |
Start Year | 2015 |
Description | Plurimes Consortium |
Organisation | Leiden University |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | Pluriomics BV |
Country | Netherlands |
Sector | Private |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | Sapienza University of Rome |
Country | Italy |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | Stem Cell Technologies |
Country | Canada |
Sector | Private |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
Country | Switzerland |
Sector | Public |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | University College London |
Department | UCL Cancer Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | University of Cambridge |
Department | Cavendish Laboratory |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | University of Dresden |
Department | Biotechnology Center |
Country | Germany |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | University of Sheffield |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Description | Plurimes Consortium |
Organisation | University of Strasbourg |
Country | France |
Sector | Academic/University |
PI Contribution | From the Plurimes project website: "The PluriMes Project: Pluripotent stem cell resources for mesodermal medicine. A consortium of 12 European partners have been awarded €6million by the European Commission for a research and development project focused on directing stem cells to become bone and muscle. Pluripotent stem cells have the potential to generate any type of cell found in the body. They are generated and multiplied in the laboratory. By harnessing the capacity of pluripotent stem cells to produce functional cell types with precision and at scale, researchers hope to enable new treatment modalities for degenerative diseases. The PluriMes project is specifically targeted at therapies for muscle, bone and cartilage. The project combines the expertise of ten academic and two industrial partners to bring together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. PluriMes is supported through the European Commission's Framework 7 HEALTH research programme and Coordinated by Professor Austin Smith from the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge." My tem and I are key members of this consortium of top European stem cell researchers and our role focuses on the development of pluripotent stem cell based technologies for skeletal muscle disease modelling, drug development, cell therapies and tissue engineering. |
Collaborator Contribution | Please refer to the project's website for details on specific expertise and contributions: https://www.plurimes.eu |
Impact | The collaboration is multidisciplinary, including also SMEs/Biotech companies. Several outputs have resulted from this partnership, including several publications (most of which listed here in ResearchFish associated to the specific awards), successful outreach activities (e.g. Pint of Science Festival 2015) and promising scientific collaborations (e.g. development of the first human pluripotent stem cell-derived artificial muscle tissue - confidential). |
Start Year | 2014 |
Title | METHOD FOR OBTAINING MAB-LIKE CELLS AND USES THEREOF |
Description | The invention relates to the derivation of mesoangioblast-like (MAB-like) cells from pluripotent cells such as induced pluripotent (IPS) and embryonic stem (ES) cells, to cells obtained thereby and to medical uses of such cells, in particular in the treatment of muscular dystrophies. |
IP Reference | WO2013108039 |
Protection | Patent application published |
Year Protection Granted | 2013 |
Licensed | No |
Impact | Industry-Academia collaboration with Takeda Pharmaceuticals funded via their New Frontier Science scheme. |
Title | Co-Investigaor in first-in-human cell therapy clinical trial |
Description | Allogeneic cell therapy for Duchenne muscular dystrophy |
Type | Therapeutic Intervention - Cellular and gene therapies |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2015 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | Further pre-clinical studies are ongoing to move towards a similar autologous strategy, including development of novel gene correction approaches (HACs, lentiviral mediated exon skipping) both at UCL and University of Manchester, where a second clinical trial is also currently being designed (funded by the Wellcome Trust to Prof Giulio Cossu). |
URL | http://embomolmed.embopress.org/content/7/12/1513.long |
Title | Mesoangioblast-mediated exon skipping for genetic correction of exon 51 mutation, based upon a single injection in individual skeletal muscles of five non ambulant patients affected by Duchenne Muscular Dystrophy: a non randomized, open label, phase I/IIa study. |
Description | Mesoangioblast-based gene therapy for Duchenne Muscular Dystrophy: a phase I/IIa study / DMD04 (DMD05) Background We pioneered cell therapy for muscular dystrophy with mesoangioblasts (MABS), vessel-associated myogenic progenitors, able to cross the endothelium when delivered intra-arterially and thus distribute evenly to dystrophic muscle. After satisfactorily testing the protocol in three mouse and one dog model of muscular dystrophy and toxicity studies, five DMD (age 8-12, two wheelchair-bound) were selected for a first-in-human, exploratory, prospective, non-randomized open-label phase I-IIa clinical trial of intra-arterial HLA-matched donor MABS transplantation (Eudract Number: 2011-000176-33). The trial proved safety but not efficacy, at variance with results obtained in pre-clinical models (Cossu et al. EMBO Mol. Med. 2015). Among relevant factors were the advanced age of patients and consequent low engraftment that should improve in younger patients. Even so, the level of engraftment will probably remain below the threshold of clinical efficacy. In order to approach and eventually reach clinical efficacy, several steps are being taken to implement the transplantation protocol. Among these, we moved to autologous cells, genetically corrected with a lentiviral vector expressing a small nuclear RNA (U7) engineered to recognize and skip exon 51. In other words this would be a cell-mediated exon skipping. Importantly, the snRNA from genetically corrected autologous cells should correct also neighboring nuclei, inside multinucleated fibers, and thus multiply the therapeutic effect. This novel protocol needs to be first tested locally for safety reasons and this will be done in this study. Study design The study will be a single centre, prospective, sequential, non-randomised, open-label clinical phase I-II study of cell-mediated gene therapy for DMD with autologous, genetically corrected human mesoangioblasts (auto-MABS). 1. Mesoangioblasts will be isolated from a small foot muscle (EBD) of one non-ambulant patient, with a skippable mutation in exon 51, as a separate protocol (DMD05), necessary to validate the SOPs and prepare an IMPD to be submitted to MHRA. The cells will be transduced with a GMP lentiviral vector expressing a small nuclear RNA engineered to skip exon 51, thus restoring the dystrophin reading frame. Transduced cells will be tested for proliferation, differentiation, chromosome abnormalities, pro-vector insertion sites and tumour formation in SCID/bg mice. 2. This patient will be offered the possibility of participating in the subsequent trial (DMD04). 3. Four patients (+ the one of DMD05) will be recruited and undergo a biopsy (except Patient #1 who will have already done it). As in DMD05, cells will be transduced and characterised as in DMD05. 4. After successful completion of the pre-clinical work, cells will be injected into the contra-lateral EBD. After three months a biopsy of the injected muscle will analyse engraftment of transplanted cells and dystrophin production. 5. If dystrophin accumulation is = 10% of a healthy muscle, cells will be subsequently injected in the muscles of the thumb, whose force of contraction will be measured. While safety will represent the primary outcome, increased force of the thumb might improve the quality of the patient's life. Study Objectives: 1. Safety: To assess the incidence of adverse events (any grade) in DMD patients treated with intra-muscular (foot and hand) injections of auto-MABS after genetic correction with a lentiviral vector expressing a small nuclear RNA engineered to skip exon 51 of the dystrophin gene. 2. Efficacy: A) To determine the effect of a single intra-muscular injection into the foot EBD of genetically corrected auto-MABS in inducing cell engraftment and dystrophin synthesis. B) To determine the ability of genetically corrected auto-MABS to increase the force of contraction of the thumb after single intra-muscular injections in the Adductor pollicis, Opponens pollicis, Abductor pollicis brevis and Flexor pollicis brevis of the dominant hand. Contributors: 1. University of Manchester, Institute of Inflammation and Repair: study coordination. G. Cossu (PI), pre-clinical work and analysis of biopsies (QT-PCR). Urmaas Rostalu, Francesco Galli, Bashar Aldeiri, Laricia Braggs, Alessandra Albertini (team). 2. Royal Manchester Children Hospital and NIHR / Wellcome Trust Manchester Clinical Research: Clinical work. Patient selection, treatment and follow up. Analysis of clinical endpoints. Imelda Hughes (Clinical Chief Investigaror) and Gary McCullagh. 3. Institute of Child Health, UCL: Study design, Analysis of biopsies (IF and WB) expertise in muscle cell biology. Francesco Muntoni, Silvia Torelli, Jennifer Morgan 4. University of Manchester, Cleanrooms, Core Technology Facility: isolation, expansion and characterization of MABS as Investigational Medicinal Product. Sue Kimber and Joan Benson. 5. GMP facility at the Denmark Hill campus, KCL. GMP Lentiviral production. Farzin Farzaneh, and Rebecca Prue. 6. The Cell Therapy Catapult. Regulatory aspects. Jacqueline Barry. 7. UMIP (University of Manchester Intellectual Property), Commercialization. Arnaud Garçon. |
Type | Therapeutic Intervention - Cellular and gene therapies |
Current Stage Of Development | Initial development |
Year Development Stage Completed | 2016 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | The trial will have as first end point dystrophin production. If after cell injection, we will be able to measure an amount of dystrophin which is 10% or more of a healthy muscle, we will inject other cells, similarly corrected in the thumb of the same patient. An increase of force of contraction would greatly benefit the quality of every day life in patients. Moreover this outcome would set the basis for a subsequent trial, this time in very young patients with systemic distribution and a defined "intent to cure" |
Description | "Lunch and Learn" talk at Muscular Dystrophy UK |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | "Lunch and Learn" talk at Muscular Dystrophy UK headquarters, London, March 2020. Talk streamed nationally to other MDUK sites followed by interview to be posted online on MDUK website and Twitter account. |
Year(s) Of Engagement Activity | 2020 |
Description | - Muscular Dystrophy UK research strategy reviewing panel, Jan 2018 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Muscular Dystrophy UK research strategy reviewing panel |
Year(s) Of Engagement Activity | 2018 |
Description | 19th London Myology Forum, Imperial College London (UK), Jun 2017 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Oral presentation at London Myology Forum |
Year(s) Of Engagement Activity | 2017 |
Description | AFM - Action Duchenne - Muscular Dystrophy UK expert group on cell therapy, Jun 2017 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | AFM - Action Duchenne - Muscular Dystrophy UK expert group on muscle cell therapy |
Year(s) Of Engagement Activity | 2017 |
Description | AFM-Telethon Conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation at AFM-Telethon Myology 2022 Conference, Nice (FR), Sep 2022 |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.myology2022.org |
Description | Action Duchenne annual conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Action Duchenne annual conference, Hinckley, UK, Nov 2019 |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.actionduchenne.org/annual-international-conference/adconf19/presentations/ |
Description | Apollo Society London, launching event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Apollo Society London (launching event). Please see: http://london.apollosociety.eu |
Year(s) Of Engagement Activity | 2018 |
URL | http://london.apollosociety.eu |
Description | Conference of patients affected by Duchenne Muscular Dystrophy and their families |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | XIII INTERNATIONAL CONFERENCE ON DUCHENNE AND BECKER MUSCULAR DYSTROPHY 21 - 22 February 2015, The Church Palace, Rome - Italy |
Year(s) Of Engagement Activity | 2015 |
Description | EMBO Conference "Stem Cells & Regenerative Medicine", Heidelberg (DE), May 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Oral presentation at one of Europe's most prestigious conferences on stem cells |
Year(s) Of Engagement Activity | 2017 |
Description | European Society of Gene and Cell Therapy, 2017 Congress, Berlin (DE), Oct 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Three invited oral presentations from the Tedesco lab to this prestigious gene and cell therapy conference |
Year(s) Of Engagement Activity | 2017 |
Description | Invited presentation at Institute Mondor, Creteil, France |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Paris Est - Creteil University Medical School, Paris (FR), Sep 2018 |
Year(s) Of Engagement Activity | 2018 |
Description | Invited presentation at Institute Pasteur, paris |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Institut Pasteur, Paris (FR), Sep 2018 |
Year(s) Of Engagement Activity | 2018 |
Description | Invited presentation at Kyoto University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Center for iPS Cell Research and Application (CiRA), Kyoto University (JP), Sep 2018 |
Year(s) Of Engagement Activity | 2018 |
Description | Invited presentation at international chromosome conference |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Chromosome Dynamics: Emerging Concepts in Chromosome Biology, Vienna (AS), Mar 2019 |
Year(s) Of Engagement Activity | 2019 |
Description | Invited seminar at university of Barcelona |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk within the Master Programme in Gene and Cell therapy of the University of Barcelona |
Year(s) Of Engagement Activity | 2017 |
Description | Invited seminar, University of Padova |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar at the Department of Biomedical Sciences, University of Padova, Padova (IT), Jun 2022 |
Year(s) Of Engagement Activity | 2022 |
Description | Invited talk at Friedrich-Baur-Institut, University of Munich (LUM), Munich (DE), Feb 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk at Friedrich-Baur-Institut, University of Munich (LUM), Munich (DE), Feb 2018 on experimental therapies for muscle disorders. Audience of approximately 40 participants. |
Year(s) Of Engagement Activity | 2018 |
Description | Invited talk to undergraduate and graduate students of different UCL programmes |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk to undergraduate and graduate students of different UCL programmes: "Stem Cells and Regenerative Medicine" (CELL3001), 2014 onwards; "Stem Cells and Tissue Repair" (CHLDGG04), MSc in Gene & Cell Therapy, 2013 onwards; "Tissue Engineering" (MECHGB07), MSc in Tissue Engineering, 2016 onwards. |
Year(s) Of Engagement Activity | 2014,2015,2016,2017,2018 |
Description | Muscular dystrophy conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Action Duchenne annual conference, London, UK, Nov 2015. Parents of a child with muscular dystrophy approached for further information and also visited my laboratory a few weeks afterwards. |
Year(s) Of Engagement Activity | 2015 |
Description | Nature Conference on Regeneration, Milan (IT), Nov 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited oral presentation at very prestigious conference on stem cells and regeneration |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.nature.com/natureconferences/regen17/index.html |
Description | Online seminar at MDUK Neuromuscular Centre |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Online seminar at MDUK (Muscular Dystrophy UK) Neuromuscular Centre, Oxford University, UK (virtual), Oct 2021 |
Year(s) Of Engagement Activity | 2021 |
Description | Oral presentation to UCL graduate and undergraduate students |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Annual seminars on muscle stem cells and regeneration in three separate UCL modules: 1) "Stem Cells and Regenerative Medicine" (CELL3001), 2014 onwards; 2) "Stem Cells and Tissue Repair" (CHLDGG04), MSc in Gene & Cell Therapy, 2013 onwards; 3) "Tissue Engineering" (MECHGB07), MSc in Tissue Engineering, 2016 onwards. |
Year(s) Of Engagement Activity | 2013,2014,2015,2016,2017,2018 |
Description | Oxford Global 4th Annual Stem Cell Conference, London (UK), Nov 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk at stem cell conference |
Year(s) Of Engagement Activity | 2017 |
Description | Podcast interview "Stem Cells @ Lunch Digested" |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Prof Francesco Saverio Tedesco, Professor of Neuromuscular Biology and Regenerative Medicine at University College London, is interviewed by researcher Dr Davide Danovi. Francesco talks about his work using stem cells to understand and develop new therapies for muscular diseases such as muscular dystrophy. He speaks about the balance between his professions as a clinician and a scientist, and how this supports the translational goal of his research. |
Year(s) Of Engagement Activity | 2021 |
URL | https://soundcloud.com/user-563815853/episode-127-prof-francesco-saverio-tedesco-seeing-patients-giv... |
Description | Presentation and discussion with neuromuscular patient advocacy group (Spain) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Talk sparked questions and discussion afterwards. Patients were very happy and appeared to have understood the difficulties related to the development of new therapies for genetic diseases. |
Year(s) Of Engagement Activity | 2013 |
Description | Presentation to Duchenne patient advocacy group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Improved understanding of the status of gene and cell therapy for muscular dystrophy Request for further information and also request for job placements in my laboratory from students present in the audience |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.actionduchenne.org |
Description | Presentations to patient advocacy group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Improved understanding of the status of the research field from the Duchenne patient community. Talk stimulated lively discussion afterwards. After my talk a video was generated by the charity for their website. I was contacted by several patients via email afterwards for additional information. |
Year(s) Of Engagement Activity | 2012,2013,2014 |
URL | http://www.parentproject.it/wp-content/uploads/2014/01/ProgrammaProvvisorio_14-02.pdf |
Description | STEMCELL Technologies Webinar, iPSC series (streamed live worldwide), Apr 2017 |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Webinar on iPSC series, streamed live worldwide, Apr 2017 |
Year(s) Of Engagement Activity | 2017 |
Description | Science Festival (London) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | "Pint of Science" festival (www.pintofscience.com), London, UK, May 2015. My presentation on stem cells in a local pub was also streamed by an internate radio and posted as a podcast. Several questions where asked by members of the general public. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.pintofscience.com |
Description | Seminar to general paediatricians |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | ? Weekly paediatric teaching session, University College Hospital, London, UK, Nov 2016. The clinicians reported increased interest in the subject. |
Year(s) Of Engagement Activity | 2016 |
Description | Seminar to general paediatricians |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | ? Weekly paediatric & neonatal seminar, Whittington Hospital, London, UK, Feb 2016. The clinicians reported increased interest in the subject. |
Year(s) Of Engagement Activity | 2016 |
Description | Summer School |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | XIX International Pharmacology School "Teófilo Hernando", Santander (ES), Jun 2022 |
Year(s) Of Engagement Activity | 2022 |
URL | http://www.uimp.es/agenda-link.html?id_actividad=654e&anyaca=2022-23 |
Description | Talk at Community Paediatrics Service, St. Ann Hospital, London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Talk at paediatricians of the Community Paediatrics Service, St. Ann Hospital, London on progress on neuromuscular diseases in children. |
Year(s) Of Engagement Activity | 2019 |
Description | Talk at London School of Paediatrics research evening |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | London School of Paediatrics Research Evening, London (UK), Jun 2019 |
Year(s) Of Engagement Activity | 2019 |
URL | https://londonpaediatrics.co.uk/blog/next-lsp-research-evening-monday-24th-june-at-6pm/ |
Description | Talk to patient association (Italy) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Int. Conferences on Duchenne and Becker Muscular Dystrophy, Rome, Italy. Organised by Duchenne Parent Project Onlus. Several questions where asked by patients on novel therapies for muscular dystrophy. |
Year(s) Of Engagement Activity | 2012,2013,2014 |
Description | University College Hospital Neonatal Unit, London, UK, Aug 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | University College Hospital Neonatal Unit, London, UK, Aug 2017 |
Year(s) Of Engagement Activity | 2017 |
Description | Visit to town hall and seminar on HACs for muscular dystrophy and on the topic of "brain drain" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Talk sparked questions and discussion afterwards After my talk several persons of the audience approached me to congratulate, since they had improved their knowledge in gene and cell therapy |
Year(s) Of Engagement Activity | 2014 |
Description | Winterschools |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | TERMIS/INTERREG Musculoskeletal Winterschools, Radstadt (AS), Mar 2022 and Jan 2023 |
Year(s) Of Engagement Activity | 2022,2023 |
URL | https://trauma.lbg.ac.at/news/the-termis-winterschool-2023/?lang=en |
Description | World Muscle Society 2017 annual conference, Saint Malo (FR), Oct 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Two oral presentations at one of the most prestigious international muscle conferences |
Year(s) Of Engagement Activity | 2017 |