Cell Therapy for Type 1 Diabetes
Research type
Research Study
Full title
Cell Therapy for Type 1 Diabetes
IRAS ID
193395
Contact name
Kevin Docherty
Contact email
Sponsor organisation
University of Aberdeen
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
The aim of this study is to provide an alternative supply of islets of Langerhans (islets) for transplantation in the treatment of type 1 diabetes. Islets are clusters of cells located throughout the pancreas that produce and secrete insulin. In type 1 diabetes islets are completely destroyed via an autoimmune process, and people with type 1 diabetes are dependent on multiple daily insulin injections. Recently, islet transplantation has been introduced as a viable alternative therapeutic option for a large number of people with type 1 diabetes. However, a major barrier to the widespread application of islet transplantation is the scarcity of cadaveric donor tissue. A healthy individual has about 1 million islets representing around 2% of the pancreas. The remaining part of the pancreas, the exocrine tissue, is normally discarded after the islets are isolated. We propose to reprogramme this redundant exocrine tissue into functional islets with the potential to increase the number of transplants from around 35 per year to several hundred. The cells will be reprogrammed by genetically modifying the cells to express molecules that have the ability to convert the exocrine tissue to islets. The human exocrine-enriched tissue will be provided by the Scottish islet Transplantation Centre, which is based in the Scottish National Blood Transfusion Centre in Edinburgh. The reprogramming protocol will be performed at the University of Aberdeen. To establish the reproducibility and to optimize further the protocol additional studies will be performed at the Free University in Brussels. The reprogramming protocol takes around 10 days to perform, while the study itself will last for five years with the expectation that clinical trials will be underway by 2019.\n\nIt is now well recognised that islet transplantation has a major role in the treatment of diabetes, particularly for those patients with severely impaired awareness of hypoglycaemia and frequent serious hypoglycaemic events (SHEs). However, the lack of donor cadaveric tissue has presented a significant barrier to the widespread application of islet transplantation. Our aim is to provide an alternative source of islets that fill this gap.\nThe project arose from a long-standing collaboration between Professor Docherty, a biochemist/stem cell biologist with a strong background in islet biology and Mr John Casey, a transplant surgeon who set up and now directs the Scottish Islet Transplantation Centre. Our early discussions during the period 2003 to 2008 focused on pluripotent cells as an alternative source of islets, and several publications came out of these studies. Around 2008 we began to develop our ideas concerning the potential to reprogramme the exocrine-enriched fraction that is left over from the islet isolation procedure. This work was funded by the MRC and led to a number of publications that underpin this present application.\nThe data to date suggest that the resultant cells would have a therapeutic effect following transplantation in humans. On this basis we obtained further funding from the Cell Therapy Catapult who now manage the project and have assembled a consortium of stakeholders, IsletCTS. The plan is to launch IsletCTS as a new company with the aim of taking cell therapy for type 1 diabetes into the clinic. Those involved include the University of Aberdeen, University of Edinburgh, the Scottish National Blood Transfusion Service and NHS Lothian. The Free University of Brussels has signed agreements that will allow studies to take place in their facilities. We have regular meetings in Edinburg during which we have an overview of the data and discussions that involve clinical outcomes, scaling up the protocol under clinically acceptable (GMP) conditions, health economics, toxicity and safety testing and regulatory issues. The overall plan is to commence clinical trials towards the end of 2019.\n In the main part of the study the cells will be genetically manipulated in ways that do not affect the genome. It is anticipated that in time these cells will be transplanted into patients. \n\n
REC name
London - Chelsea Research Ethics Committee
REC reference
15/LO/2206
Date of REC Opinion
29 Dec 2015
REC opinion
Favourable Opinion