Differentiation of GMP-grade human embryonic stem cells to midbrain dopaminergic neurons for transplantation

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Parkinson's disease (PD) is an incurable and progressively degenerative condition. Although the symptoms are well managed at the early stages with medication, there is currently no treatment to halt or reverse the progress of PD. In the late 1980s and 1990s several PD patients received transplants of fetal midbrain tissue containing dopamine-producing neurons. A small fraction of patients showed tremendous benefit from such grafts. A multi-centre European clinical trial led by co-applicant Dr. Roger Barker, TRANSEURO, is underway to re-visit fetal midbrain transplants and systematically address all potential problems faced in the earlier clinical trials. These trials will be small due to the limiting amount of fetal tissue available. There will be a pressing need to resolve the critical issues of scaleable supply and quality of appropriate dopaminergic neurons for any future widespread use in the treatment of PD. Replacing fetal midbrain tissue with dopaminergic neurons differentiated from human embryonic stem cells (hESCs) is the most realistic solution to this cell source problem. Currently 5 different centres in the UK (Edinburgh, London, Manchester, Newcastle, and Sheffield) have established clinical-grade hESC lines, over 15 lines in total. This proposal will examine all UK clinical-grade hESC lines and compare them for their ability to make dopaminergic neurons. We will modify and optimise a novel method to transform hESCs to dopaminergic neurons from our collaborator Dr. Lorenz Studer (Sloan-Kettering, NYC). The best performing hESC line will be used for transplantation into two distinct rat models of PD. Graft survival, behavioural improvements, and absence of tumour formation will all be carefully assessed. The success of this project using hESC-derived dopaminergic neurons in pre-clinical rat models of PD will be a significant step towards the first-in-human clinical trials.

Technical Summary

Transplantation of fetal midbrain tissue to treat Parkinson's disease (PD) has demonstrated proof-of-concept that some patients can benefit from such grafts. An international multi-centre Framework 7 European clinical trial, TRANSEURO, is underway to re-visit fetal midbrain transplants and systematically address all protocol and procedural issues with the earlier clinical trials. There is a pressing need to resolve the critical questions of scaleable supply and quality of appropriate Good Manufacturing Practice (GMP) grade dopaminergic cells for any future widespread use in the treatment of PD. Replacing fetal midbrain tissue with midbrain dopaminergic (mDA) neurons differentiated from human embryonic stem cells (hESCs) is the most realistic solution to the cell source problem. We will modify and optimise a novel method to differentiate hESCs to mDA neurons, which relies on a developmental protocol based on floor plate specification. GMP-grade hESCs from multiple sources throughout the UK will be quantitatively assessed for efficiency of mDA differentiation. The best performing hESC line will be used to establish procedures to produce GMP-capable mDA preparations for transplantation. All experiments will be performed with research-grade reagents that have a suitable GMP-grade equivalent available. The mDA neuronal populations will be transplanted into two nude rat models of PD (i) a 6-hydroxydopamine lesion model and (ii) an adeno-associated virus-alpha-synuclein model. Graft survival, behavioural improvements, and absence of tumour formation will be assessed. This collaborative proposal will bring together expertise in pluripotent stem cell differentiation, pre-clinical models of PD, and the UK 's clinical-grade hESCs, with the ultimate aim of moving to first-in-human clinical trials.

Planned Impact

Parkinson's disease (PD) is an incurable neurodegenerative disorder that affects 120,000 people in the UK and 6-8 million people world-wide, and this number is expected to increase exponentially with the aging population. The total annual burden of PD in the UK for 2007 was estimated to be £3.3 billion (Findley LJ, 2007), and this economical burden increase substantially with the increase in incidence. This project proposes to establish the foundation to bring a cell-based therapy to the clinic for PD. In the best-case scenario, the impact on the quality of life for sufferers of PD and their carers would be enormous. Although, transplantation of hESC-derived dopaminergic neurons may not provide a true cure due to multiple neural cell types affected in PD, it may provide 15-20 years of drug-free and motor symptom-free relief. Furthermore, combining a transplantation therapy with a disease-modifying drug that prevents alpha-synuclein-mediated neuronal damage may provide a near-complete cure of this condition.
The upfront costs of a transplantation therapy may be large (on par with deep-brain stimulation), but if successful, there will be substantial savings in medication costs and other types of care, including palliative care. The economic savings to the NHS could be very significant indeed.

Findley LJ. The economic impact of Parkinson's disease. (2007) Parkinsonism Relat Disord. 13 Suppl:S8-S12.

Publications

10 25 50
 
Description Cure Parkinson's Trust grant
Amount £93,061 (GBP)
Funding ID CPT8 
Organisation Cure Parkinson's Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2013 
End 05/2016
 
Description Developing an assay to measure neuron-to-neuron spread of alpha-synuclein on a microfluidcs platform
Amount £164,603 (GBP)
Funding ID BIOSCIE2009 
Organisation UCB Pharma 
Sector Private
Country United Kingdom
Start 03/2019 
End 03/2020
 
Description Hong Kong : Scotland Collaborative Research Partnerships
Amount £10,000 (GBP)
Funding ID 2014_HK-Scot-0023 
Organisation Government of Scotland 
Department Scottish Funding Council
Sector Public
Country United Kingdom
Start 01/2015 
End 12/2015
 
Description MRC Confidence in Concept
Amount £61,440 (GBP)
Funding ID MRC/CIC3/018 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2015 
End 02/2016
 
Description UCB Industrial partnership
Amount £244,031 (GBP)
Funding ID Not known 
Organisation UCB Pharma 
Sector Private
Country United Kingdom
Start 03/2016 
End 02/2018
 
Description Wellcome Trust Clinical PhD Fellowship
Amount £231,504 (GBP)
Funding ID 203646/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2016 
End 08/2019
 
Title Alpha-synuclein knock-out human embryonic stem cells 
Description We used CRISPR/Cas9 to knock-out the Parkinson's-related gene, alpha-synuclein (aSyn), in RC17 human embryonic stem cells. We generated a number of cell lines that are aSyn-null and confirmed thet are protein-null by western blotting. We have published the lines in the following paper: Chen Y, Dolt KS, Kriek M, Baker T, Downey P, Drummond NJ, Canham MA, Natalwala A, Rosser S, Kunath T. Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene. Eur J Neurosci. 2019 Feb;49(4):510-524. doi: 10.1111/ejn.14286. 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? Yes  
Impact These lines have so far been shared with Dr David Beckham at UC Denver under MTA for a collarative project, and Dr Malin Parmar at Lund University. 
URL https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14286
 
Title Protocol of cryopreservation of human dopaminergic neural cells 
Description We have released a highly optimised method for cryopreservation of human dopaminergic neural cells differentiated from human embryonic stem cells and human induced pluripotent stem cells 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact The methods and manuscript are recently released (12th February 2020), and impact is not known yet. However, these methods have been instrumental for a number of collaborations, including Dr Eilis Dowd at National University of Ireland, Galway, and Prf J. David Beckham at University of Colorado 
URL https://www.biorxiv.org/content/10.1101/2020.02.11.944272v1
 
Description Michele Zagnoni collaboration 
Organisation University of Strathclyde
Department Department of Electronic & Electrical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Dr Zagnoni and I are collaborating to combine our expertise in generating human neurons with his expertise in microfluidics. UCB Pharma are funding this project for two years (two 1-year contacts) for a total of ~£298,000.
Collaborator Contribution Dr Zagnoni is provided custom-made microfluidics devices to culture and observe isolated populations of neurons.
Impact This collaboration led to a significant industrial partnership with UCB Pharma, and a fully costed contract for two years.
Start Year 2014
 
Description 1st Intercontinental Workshop for First Clinical Stem Cell trials for Parkinson's 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact This meeting was held in London 4-5 May, 2014. My talk on clinical-grade UK human embryonic stem cells (hESCs) for Parkinson's treatment generated substantial discussion, and highlighted the unique position of the UK in bringing this type of therapy to the clinic.

After my talk a new collaboration was started with Dr. Malin Parmar (Lund, Sweden), and we plan to write joint grant applications, and we are also discussing how we mght run the first clinical trial, and whether it is advantageous to have a joint Sweden-UK trial.
The next meeting of this consortium is scheduled for 18-20 May, 2015 in New York.
Year(s) Of Engagement Activity 2014
URL http://www.gforce-pd.com/gforce-a-new-global-iniatitive-around-stem-cell-based-therapies-for-parkins...
 
Description Alliance Of Scottish Parkinson's Nurse Specialist Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Health professionals
Results and Impact I presented current research in my lab funded by Parkinson's UK, The Cure Parkinson's Trust, and the MRC. I had 4-5 insightful questions after my talk.

I received very detailed feedback from the audience including scores out of 10, and lots of written feedback. More than half the scores were 8/10, 9/10, or 10/10. Some comments were 1. A bit over my head but incredibly interesting and encouraging that they are still searching for a cure. He was very enthusiastic about his subject and extremely knowledgeable. 2. Excellent talk but more scientific than my brain could cope with. 3. Interesting but not clinical enough. 4. Very knowledgeable speaker with an obvious huge breadth of information to deliver.
Year(s) Of Engagement Activity 2014
 
Description BNA Festival 2015 Talk 1 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact On 13th April, I presented a seminar in the "Human stem cell models of neurodegenerative disease" session of the BNA 2015 Festival in Edinburgh.

Renewed collaboration with Dr Selina Wray which has led to a grant application the Wellcome Trust with Dr Michele Zagnoni (University of Strathclyde).
Year(s) Of Engagement Activity 2015
URL http://www.bna2015.org/programme/details/?session=11523&theme=G
 
Description BNA Festival 2015 Talk 2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact On 14th April I presented at talk entitled "Differentiation of clinical grade human pluripotent stem cells into midbrain dopaminergic neurons" in the "Modelling human disease in a dish: implications for understanding neurodegeneration and for development of novel therapies" session at the BNA 2015 Festival

Reinforced collaboration with Prof Meng Li and Prof Malin Parmar
Year(s) Of Engagement Activity 2015
URL http://www.bna2015.org/programme/details/?session=11534&theme=B
 
Description BioDundee Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact On 2nd June, 2015 I presented a lecture at the BioDundee conference in Dundee and entertained questions afterwards. The audience was a mix of academia, industry, and government individuals

Not aware of any impact.
Year(s) Of Engagement Activity 2015
URL http://www.biodundee.co.uk/events/3143/BioDundee+Conference+2015/
 
Description British Science Festival - Bradford 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact On 9th September, 2015, I was part of a panel discussion on the topic of getting old - "Who wants to live forever?". Prof Anthea Tinker, sociologist from KCL, James Stark, medical historian from University of Leeds, and myself consisted of the panel.

There was a tremendous amount of discussion after our short talks.
There were also some on-line press about the event that would somewhat inaccurate!
http://www.express.co.uk/news/science/604082/Vitamins-waste-of-time-fasting-live-longer
Year(s) Of Engagement Activity 2015
URL http://www.britishscienceassociation.org/Blog/new-thinking-about-getting-older
 
Description Cafe Scientifique Dunkeld 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact On 9th December, 2014 I presented by research on Parkinson's to the Dunkeld branch of Cafe Scientifique. It was followed by 30min of very stimulating discussion from the attendees.

Attendees commented after the event that I certainly removed some of the confusion around stem cells in their minds, and they were more in favour of stem cell research after my talk and discussions.
Year(s) Of Engagement Activity 2014
URL http://tulliemet-perthshire.org.uk/main/index.php/cafesci
 
Description Cafe Scientifique Edinburgh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My Cafe Scientifique talk on 14th July 2014 in Edinburgh promoted over 40min of additional discussion.

The organiser recieved an email from a participant stated it was one of the most engaging Cafe Scientifique he had attended.
Year(s) Of Engagement Activity 2014
 
Description Cardiff seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I presented my current research to a group of 40-50 basic and clinician scientists at Cardiff University.

I have positive feedback on my lecture from my host Dr. William Davies. I also had useful post-seminar discussions with Prof Anne Rosser about scientific direction.
Year(s) Of Engagement Activity 2013
 
Description Co-host 2015 Edinburgh Parkinson's Lecture - Patrick Brundin 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Supporters
Results and Impact On 22nd April, I co-hosted Patrik Brundin's Edinburgh Parkinson's Lecture with Prof Ken Bowler. I also organised a showcase of Edinburgh researchers for Arthur Roach and Patrik Brundin to hear about. They included Prof Manfred Auer, Prof Kathryn Ball, Dr Thomas Becker, Dr Alison Hulme, Dr Maria Doitsidou, Dr Lysimachos Zografos of Parkure Ltd, and myself.

Lots of ideas were exchanged and led to a collaboration between Patrik Brundin and Dr Zografos, and initiated a collaboration with Dr Doitsidou and myself.
Year(s) Of Engagement Activity 2015
URL http://www.edinburghparkinsons.org/edinburgh-parkinsons-lecture-2015/
 
Description Co-host 2018 Edinburgh Parkinson's Lecture - Giovanna Mallucci 
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 Co-hosted, with Prof Ken Bowler, the 2018 Edinburgh Parkinson's Lecture by Prof Giovanna Mallucci on 17th September 2018 at the Royal College of Physicians Edinburgh. About 300 Parkinson's patients, carers, and general public attended.
Year(s) Of Engagement Activity 2018
URL https://www.edinburghparkinsons.org/video-of-the-2018-parkinsons-lecture/
 
Description Co-host 2019 Edinburgh Parkinson's Lecture - Andres Lozano 
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 Co-hosted Prof Andres Lozano Edinburgh Parkinson's Lecture with Prof David Melton on 30th September 2019 at the Royal College of Physicians Edinburgh. About 300 people, many with Parkinson's, attended. I organised his schedule including meeting with the Tayside neurosurgeons regarding Functional Neurosurgery services in Scotland.
Year(s) Of Engagement Activity 2019
URL https://www.edinburghparkinsons.org/edinburgh-parkinsons-lecture-2019/
 
Description Congress on the Italian (ABCD) Association of Cell Biology and Differentiation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited speaker at conference and excellent questions after mu presentation

Renewed collaboration with Dr Luciano Conti at the University of Trento
Year(s) Of Engagement Activity 2015
URL http://abcd2015.azuleon.org/welcome.php
 
Description Dalriada Conversations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact On 25th November 2016, I gave a 40 minute talk on stem cells and potential applications for Parkinson's disease. This was followed by 60min of questions and discussions. Prof Ken Bowler (Edinburgh branch of Parkinson's UK) is one of the co-organisers of Dalriada Conversations and set up the invitation to speak. Nick Stroud, another co-organiser, sent me a card in the post dated 26th November that read "Dear Tilo, Just a wee note to thank you very much for giving up your evening to come and have a chat with us in Portobello. Your work is fascinating, and you have a very engaging way of talking about it. And even though you made it sound really challenging work, right at the frontiers of human knowledge, I think you spared us several layers of just how complicated and minutely detailed this work is! We all appreciated this from a very personal point of view, as well: it's good to know that our dear Ken has so much talent on his side. I'm sorry we kept you from your family, so appreciate your visit even more. And we certainly all wish you the very best with your continuing research. Thank you!! Nick Stroud"

At the end of the discussions I met the mother of researcher at UCL that has recently spun out a company that works on molecules that may have therapeutic potental for Parkinson's. I gave the woman my contact details, and asked for he daughter to get in contact with me.

On 8th December, 2015 I received an email from Dr Jemma Gatliff introducing herself as the daughter of the woman I meet at Dalriada Conversations on 25th November. She is the CEO and co-founder of Keregen Therapeutics, a spin-out compnay of UCL that has developed small molecule activators of NRF2, a transcription factor that activates antioxidant defense pathways. Her company is a OneStart 2015 finalist for Europe, which picks the top 10 start-up companies in the life sciences and healthcare sector for that year.
Dr Gatliff and I had our first in-person meeting on 28th December, 2015 at our institute MRC Centre for Regenerative Medicine, to share our respective knowledge and data. We also discussed how we could work together and options for potential funding. The next meeting be in her labs in London.
Year(s) Of Engagement Activity 2015
 
Description Edinburgh Fringe Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact John MacPhee and I put on a single show on 6th August 2017 as part of the Cabaret of Dangerous Ideas (CODI) series in the Edinburgh Fringe Festival. Over 110 tickets were sold, and we were the 3rd largest audience for the CODI series. Lots of very interesting discussion occurred during the event and afterwards, and we have been invited for a repeat performance on 14th February 2018 to the Edinburgh Branch of Parkinson's UK.
Year(s) Of Engagement Activity 2017
URL https://edinburghfestival.list.co.uk/event/775782-eradicate-parkinsons/
 
Description Edinburgh Parkinson's Lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact I have co-organised all the Edinburgh Parkinson's Lecture with Parkinson's UK (Ken Bowler) and the Scottish Parkinson's Nurses Association. It was presented by Prof Roger Barker (2012), Prof Ray Chaudhuri (2013), and Prof Anthony Schapira (2104) at the Royal College of Physicians to over 300 people on each occasion. The audience consisted of people with Parkinson's, their partners/relatives, caregivers, and scientists.

These presentations have major impacts to the Parkinson's patients in attendance and their loved ones. The weblink highlights for the 2013 lecture notes a quote from Shona Lawson (Support Worker from West Lothian). A patient in her area told her that lecture gave her the confidence to pick up the phone to my nurse and ask for some non-motor issues to be addressed.
Year(s) Of Engagement Activity 2012,2013,2014
URL http://www.edinburghparkinsons.org/the-edinburgh-parkinsons-lecture-2013-2/
 
Description Gavin Hastings and Warren Gatland visit to research lab 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact On 8th March, 2017 I hosted a lab visit for Gavin Hastings (Scottish International Rugby player) and Warren Gatland (coach of the British and Irish Lions Rugby team). The visit was to learn more about a cell therapy for Parkinson's (projected funded by the MRC), raise awareness for Parkinson's and to support the charity The Cure Parkinson's Trust. A BBC television crew filmed the event and it appeared on the 6 o'clock news on 8th March, 2017.
Other on-line print and video (YouTube) was also used to capture the event.
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=tvPDFibrDAo&t=1s
 
Description Host Parkinson's Research Interest Group-Counsel 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact This Edinburgh Research Interest Group meeting took place on Saturday, 8th February, 2014 at the MRC Centre for Regenerative Medicine. The invited speaker was Dr. Carl Counsel from Aberdeen speaking about his project "What changes happen over time for people with Parkinson's and their carers?" I co-hosted and facilitated this meeting with Prof Ken Bowler, the Chair of this Research Interest Group. The audience consisted of 32 people, including about people with Parkinson's and their partners. The seminar and questions was followed by an informal lunch and general discussions.

The feedback from the patients and partners/carers was extremely positive. We received a realistic picture of the true prognosis of a Parkinson's diagnosis. The group was also strengthened in their resolve to change NHS practices in the Lothian area to improve care especially in the later stages of this condition.
Year(s) Of Engagement Activity 2014
URL http://www.edinburghparkinsons.org/talk-dr-carl-counsell/
 
Description Menzies Trust 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach National
Primary Audience Supporters
Results and Impact Hosted a visit of two representatives from the J Macdonal Menzies Trust at the MRC Centre for Regenerative Medicine on Friday, 20th September, 2013.

Two representatives from the J Macdonal Menzies Trust have made sizable donations to Parkinson's UK it specifically support my lab.
Year(s) Of Engagement Activity 2013
 
Description Organiser and host of Edinburgh Research Interest Group on 12th January 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact I invited a researcher, Dr Thanasis Tsanas, to speak with Parkinson's patients and carers, and nurse specialists at the Edinburgh Research Interest Group at my workplace - the MRC Centre for Regenerative Medicine at the University of Edinburgh. The intended purpose was to inform PD patients living in Lothian of the research going on in Dr Tsanas' group. His PhD student, Anne Steinberg, also spoke and advertised that she is recruiting patients to participate in a research study.
A number of people expressed interest in participating in Anne's study. And one individual, Alison Williams, is already in email communication with Dr Tsanas to run a pilot version of the pilot and refine aspects of it.
Year(s) Of Engagement Activity 2019
URL https://www.edinburghparkinsons.org/research-interest-group/
 
Description Parkinson's UK branch visit - Falkirk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact On 16th September, 2014 I spoke to over 50 people with Parkinson's and their families about the latest research in my lab funded by Parkinson's UK, the Cure Parkinson's Trust, and the MRC. A considerable amount of questions were asked after my talk, and later one-to-one.

The organisers informed me they were very pleased with my talk, and will continue to raise funds towards my project.
Year(s) Of Engagement Activity 2014
 
Description Parkinson's disease Global Force Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I presented our unpublished work on clinical-grade human embryonic stem cells (hESCs) and received a tremendous amount of feedback from my peers.

This meeting reinforced my collaborations with Prof Roger Barker and Prof Malin Parmar, and sparked new collaborations with Prof Stephen Dunnent and Dr Jun Takahashi.
A Perspective about this meeting was published in npj Parkinson's Disease entitled "G-Force PD: a global initiative in coordinating stem cell-based dopamine treatments for Parkinson's disease"
http://www.nature.com/articles/npjparkd201517
Year(s) Of Engagement Activity 2015
URL http://www.gforce-pd.com/
 
Description Parkinsons UK branch visit - Stewartry Support Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact On 14th April, 2012 I traveled to Castle Douglas, Scotland to give a presentation about my research and meet Parkinson's patients and their families. About 30 people were in attendance.

Feedback from my presentation was very positive, and they donated £2,000 to Parkinson's UK in November 2012 towards my project (F-0902).
Year(s) Of Engagement Activity 2012
 
Description Presentation at Parkinson's UK Reseach Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact The talk was presented by Dr. Maurice Canham, the post-doctoral lead on the human embryonic stem cell (hESC) transplantation project. Discussion was generated around the unique position of the UK because of the large number of clinical-grade hESC lines available.

A notable impact was discussion with Matthew Durdy, the Chief Business Officier for Cell Therapy Catapult. We have initiated discussions around cryopreservation of cells for clinical translation, and we plan to work together on this project
Year(s) Of Engagement Activity 2014
URL http://www.parkinsons.org.uk/content/parkinsons-uk-research-conference
 
Description Roslin Institute Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I presented a seminar of my current research to 50-60 basic and veterinary scientists on 20th November, 2013 at The Roslin Institute.

I had very stimulating discussions after my seminar, including an excellent experimental suggestion from a PhD student. I am now implementing the idea into one of my projects.
Year(s) Of Engagement Activity 2013
 
Description Scottish Parliament 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact 16 MSPs attended including the Public Health Minister for Scotland. Other Parkinson's researchers and patients and carers also attended.

I made a connection with a scientist in Dundee that will lead to a visit from one of his new recruits to my lab. I also discussed with a clinican scientist in Glasgow about accessing his patient cohorts for a new biomarker study in my lab.
Year(s) Of Engagement Activity 2013
 
Description The Stem Cell Podcast Ep. 59 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact On 4th December, 2015 I discussed the issue of clinical-grade human embryonic stem cells (hESCs) for therapeutic applications for Parkinson's with The Stem Cell Podcast hosts Dr Christopher Fasano and Dr Yosif Ganat. This is in relation to our recently published paper in Scientific Reports entitled "The molecular karyotype of 25 clinical-grade hESC lines."
The podcast went live on 8th December, 2015 and I subsequently received emails from researchers complimenting me on the discussing, including from the Pasteur Institute.

On 24th December, I received an email from Shaun Teacher regarding The Stem Cell Podcast, which he listened to. He works for BioTime, Inc, a California-based company that has the commerical rights for clinical-grade human embryonic stem cell (hESC) lines established by Jeremy Crook in Singapore. We are in discussions now about how my academic work and their commercial work can work together to bring these cell lines into industrial us in the United States.
Year(s) Of Engagement Activity 2015
URL http://stemcellpodcast.com/ep-59-clinical-grade-featuring-dr-tilo-kunath
 
Description Tsukuba PhD week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I hosted 10 PhD student from the University of Tsukuba, Japan during the week of 16th-20th September, 2013. This was called the Edinubrgh-Tsukuba Summer School. Organised presentations of the PhD students and also members of MRC CRM and from other parts of the University of Edinburgh.

A notable and unexpected result of this hosting was an offer from the University of Tsukuba to generate a genetically mutant mouse of my mice free-of-charge.I have provided them with details to make a Parkinson's model, and they will have made the animals in late 2013, and they will ship mutant sperm to us in March 2014.
Year(s) Of Engagement Activity 2013
 
Description University of Toronto Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact On 10th April I presented a lecture at the 20th Anniversary Symposium of the Collaborative Program in Developmental Biology at the University of Toronto.

Not aware of any impact.
Year(s) Of Engagement Activity 2015
URL http://www.moleculargenetics.utoronto.ca/announcements/2015/7/29/cpdb-20th-anniversary-symposium