Diabetes Research Group

Clinical islet transplantation

Stephanie A Amiel, BSc, MD, FRCP RD Lawrence Professor of Diabetic Medicine King’s College London School of Medicine

Treatment of organ failure?

• Renal failure • Kidney transplant • Liver failure • Liver transplant • Heart failure • Heart transplant • Islet failure

Case Histories

1. Born 1944; T1DM 1966; keen runner

“afraid to be in charge of my granddaughter”

2. Born 1965; T1DM 1987; HCA on locked ward

“ threatened with medical redundancy”

3. Born 1985; T1DM 1994; mother of two

“ you just drove across a red light, Mummy”

GLUCOSE-RESPONSIVE INSULIN DELIVERY

Bionics vs nature?

Nature – whole pancreas or islets?

Islet Transplantation

• 1998 established laboratory • 2000 proof of concept • 2002 1 st UK patient • 2008 NCG funded programme

CITR Islet Alone Recipients outcome From all infusions

60 50 40 30 20 10 0 Month 6 N=249 Recipient Status *C-peptide data not available at Day 75 **Year 3 status independent of re-infusion Year 1 N=225 Year 2 N=169 Year 3 N=129 Insulin Independent Insulin Dependent with Detectable Fasting C-peptide No Detectable Fasting C-peptide Missing Data Insulin Independence, Insulin Dependence, Graft failure

SEVERE HYPOGLYCEMIA FOLLOWING LAST TRANSPLANT

100 90 80 30 20 10 0 70 60 50 40 Pre Inf 1 N=262 Day 30 N=262 Month 6 N=249 Year 1 N=225 No severe hypoglycemic episodes Severe hypoglycemic episode Missing data for recipient without islet graft function Missing data for recipient with islet graft function Year 2 N=169 Year 3 N=129 CITR 2007

Clinical Outcomes: Diabetes UK patients • 3 people achieved insulin independence • 1 person with 4% reduction in HbA1c • 2 people back in work • 1 woman resumed running and babysitting her grandchildren • 2 children safely back on school run

UK ITC

NCG: April 2008 2 isolation centres 6 Transplant centres Intractable hypoglycaemia Islet after kidney Local and remote Shaw, Manus, Amiel, Huang

Problems to be solved

• Current • Organ supply/distribution • Sub-optimal immunosuppression • Research • Prevent loss of islets on administration • Improve immunosuppression • Make new islets to give greater loads and re transplant if required

Meanwhile

• Whatever cell therapy we devise, it will need to be safer than insulin therapy • For a small number of patients, it already is