Manufacturing of iPS cell derived neurons from patients with familial Alzhiemer's disease for drug discovery and stratified medicine applications
Lead Research Organisation:
University of Manchester
Department Name: Dentistry
Abstract
Progress in understanding many diseases has been hindered by a lack of suitable in vitro models, particularly for diseases in which affected cell types are difficult to access or obtain. Induced pluripotent stem cells (iPSCs) are an ideal alternative source as they can be derived from patients' skin cells and have the potential to form any cell type in the body. However, current technologies are hindered by the inability to reliably produce mature cell types. We have developed a method that enables iPSCs to be reliably differentiated at low cost and high purity into neurons. This offers the ability to utilise these cells for understanding Alzheimer's disease (AD) in the petri dish and developing new treatments and diagnostics for such patients. Ultimately, we aim to produce a technology capable of diagnosing AD and informing treatment options for patients as well as providing industry with the ability to screen and develop novel drugs for this incurable disease.
Publications
Dou R
(2015)
High throughput cryopreservation of cells by rapid freezing of sub-µl drops using inkjet printing--cryoprinting.
in Lab on a chip
Hawkins K
(2014)
Novel Cell Lines Isolated From Mouse Embryonic Stem Cells Exhibiting De Novo Methylation of the E-Cadherin Promoter
in Stem Cells
Mohamet L
(2014)
Familial Alzheimer's disease modelling using induced pluripotent stem cell technology.
in World journal of stem cells
Segal JM
(2017)
Novel peptides for deciphering structural and signalling functions of E-cadherin in mouse embryonic stem cells.
in Scientific reports
| Description | TSB Stratified Medicine strategy on neurodegenerative diseases workshop October 2013 |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Call for neurodegenerative diseases funded |
| Description | Crack-It UnTangle NC3Rs |
| Amount | £81,956 (GBP) |
| Funding ID | 35529-259127 |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2013 |
| End | 06/2014 |
| Description | DPUK: Integrated Dementia Research Environment |
| Amount | £6,091,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2015 |
| End | 09/2016 |
| Description | IAA Concept study |
| Amount | £62,537 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2015 |
| End | 09/2015 |
| Description | Proximity to Discovery Secondment Grant |
| Amount | £57,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 05/2016 |
| Description | UK UKDP: Integrated Dementia Research Environment |
| Amount | £2,329,271 (GBP) |
| Funding ID | MR/M009076/1 |
| Organisation | Medical Research Council (MRC) |
| Department | Medical Research Foundation |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 09/2016 |
| Title | Differentiation of iPSCs to neural progenitor cells |
| Description | Small peptides developed during this grant has been used to derive homogeneous populations of neural progenitor cells from iPSCs (human and mouse). |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | NC3Rs Phase 1 grant award for the development of a Tau cell model |
| Title | Peptide development |
| Description | Small peptides have been developed during this grant that enable modification of gene transcript expression in embryonic stem cells |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | Several papers published by me and collaborators published |
| Title | Microarray analysis of E-cadherin inhibition in cells |
| Description | Microarray analysis of E-cadherin inhibition in mouse and human ES cells and mammary epithelial tumour cells has been analysed |
| Type Of Material | Database/Collection of data |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | Evidence that E-cadherin plays a major part in regulating signalling pathways, proliferation and apoptosis in ES and tumour cells |
| Description | Dr Richard Wade-Martins |
| Organisation | University of Oxford |
| Department | Department of Biochemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Confidential |
| Collaborator Contribution | Confidential |
| Impact | Manuscript in preparation |
| Start Year | 2013 |
| Description | Imagen-biotech |
| Organisation | Imagen Biotech |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Provision of iPS cells derived from Alzheimer's disease patients for use in drug screening applications. |
| Collaborator Contribution | Development of an Alzheimer's disease drug screening platform |
| Impact | Technology still in development |
| Start Year | 2012 |
| Description | Prof Ben Whalley |
| Organisation | University of Reading |
| Department | School of Pharmacy Reading |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Confidential |
| Collaborator Contribution | Confidential |
| Impact | Manuscript currently being written |
| Start Year | 2013 |
| Title | CELL DIFFERENTIATION |
| Description | Provided is a method of producing neural precursor cells, in which an inhibitor of E-cadherin activity is provided to a population of the cells having neural potential, cell stress is induced among the population of cells; and the surviving cells are cultured until neural precursor cells are produced. Also provided is a method of adapting a cell in vitro for therapeutic use, in which an inhibitor of E-cadherin activity is provided to a population of cells having neural potential, cell stress is induced among the population of cells, and the surviving cells are cultured until neural precursor cells are produced. This method may optionally additionally involve culturing the neural precursor cells until neural cells are produced and formulating the neural precursor cells or neural cells in a composition suitable for administration to a patient. The invention also provides cells produced by these methods. The methods may be practiced on stem cells, particularly iPSCs. The cells and methods have utility in applications including stratified medicine. |
| IP Reference | WO2014072720 |
| Protection | Patent application published |
| Year Protection Granted | 2014 |
| Licensed | Yes |
| Impact | Non-exclusive research licence awarded to Imagen-Biotech Ltd |
| Title | Alzheimer's disease diagnostic |
| Description | Alzheimer's disease diagnostic |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2012 |
| Development Status | Actively seeking support |
| Impact | None |
| Company Name | Stratastem |
| Description | Stratastem develops therapeutics for Alzheimer's disease based on neural stem cells, as well as diagnostics for the disease that detect changes in neuronal pathology. |
| Year Established | 2012 |
| Impact | Biotech Start-up |
| Website | http://stratastem.weebly.com |
| Description | Invited lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | MSCA Annual Scientific Meeting, 8th December 2015, Sheffield University, UK. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Invited lecture: Stem Cells in Drug Discovery conference, 2-3 June 2015, Cambridge University, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Stem Cells in Drug Discovery conference, 2-3 June 2015, Cambridge University, UK |
| Year(s) Of Engagement Activity | 2015 |
| Description | Invited research talk. Uppsala University, Sweden. 13th May 2015. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited research talk. Uppsala University, Sweden. 13th May 2015. |
| Year(s) Of Engagement Activity | 2015 |
| Description | TSB Stratified Medicine strategy on neurodegenerative diseases workshop. October 2013 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Discussion/workshop on TSB Stratified Medicine strategy on neurodegenerative diseases Recommendations made |
| Year(s) Of Engagement Activity | 2013 |