What is Diabetes
Diabetes mellitus is a chronic disease characterised by high blood glucose due to inadequate insulin production and/or insulin resistance which affects 382 million people worldwide, causing an estimated 5.1 million deaths in 2013 alone. Type I diabetes (T1D) is characterised by autoimmune destruction of β-cells within the pancreatic islets, resulting in lifelong inadequate insulin secretion. Type II diabetes (T2D) usually involves the stress-induced loss of β-cells due to the overwhelming insulin demand placed on them by persistent high blood sugar.
Constant high blood sugar has many negative effects including:
is a very promising therapy that has the potential advantage of re-establishing naturally-regulated insulin production. With this technique, pancreatic islets are harvested from donor pancreases and delivered to the liver by a catheter via the portal vein. Once in the liver the islets engraft and begin to produce insulin in response to blood glucose levels.
Following islet transplant, 50% of patients do not need to take insulin injections for 5 years or more and never again have dangerous unaware hypoglycaemic attacks. However, many islets are lost during and after transplantation due to lack of suitable support matrix, lack of an early oxygen supply and unfavourable inflammatory conditions within the blood vessels of the liver. As a consequence, 2-3 donor pancreases are needed to get enough islets to reverse diabetes. Furthermore, the patient must take lifelong immunosuppressive medications, which have significant negative side effects and therefore islet transplant therapy is currently only approved for the most at risk “brittle” T1D patients , or patients already on immunosuppression.
The main challenge for DRIVE is to improve pancreatic islet transplant therapy for diabetes mellitus achieving sufficient delivery, retention and maintaining survival, engraftment and functioning of newly implanted islets. DRIVE will prevent the main factors contributing to islet graft loss.
|The challenge||The DRIVE solution|
|Hypoxia due to inadequate early vascularisation||β-Gel contains oxygen producing compounds thus supplying the islets with oxygen over the first week while they are most vulnerable|
|Insufficient retention due to lack of a suitable support matrix||β-Gel is a pancreo-mimetic gel that provides a suitable support matrix to the islets|
|Inadequate extracellular matrix (ECM) cues at the site of transplantation||Specific ECM molecules acting as efficacy cues will be included in the β-Gel|
|Inflammatory reaction at the delivery site||β-Shell will be a protective and retentive macroporous capsule for the tuneable&localised delivery of the current standard of care immunosuppressive/anti-inflammatory drugs|
|Allo- and autorejection||The hydrogels will carry immunoprotective agents and efficacy cues with controllable release to potentiate the survival and decrease the time to efficacy of the islets|