• 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:

    • Retinopathy (damage to blood vessels in the eye, which can lead to blindness )
    • Nephropathy (damage to the kidneys, which can lead to renal failure )
    • Neuropathy (damage to nerves, which can lead to loss of balance, numbness and diabetic foot disease ; swelling, ulceration and infection of the foot which may necessitate amputation)
    • Cardiovascular disease (which kills 50% of people with diabetes)



  • What is insulin therapy

    Exogenous insulin administration

    has proven effective for the management of T1D and insulin-dependent T2D, but requires onerous monitoring of blood glucose to prevent hypoglycaemia.

     

    current treatment

  • Islet transplantation

    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.


    Transplanting islet cells

    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.

  • Challenges

    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

    Our Excellence

     This project has received funding from the EU Horizon 2020 research and innovation programme. Grant agreement No 645991