Research

Our mission at Semma is to cure type 1 diabetes (T1D), which affects over 1.5 million people in the US alone. T1D is an autoimmune disease in which the insulin-producing beta cells of the pancreatic islets are unable to provide enough insulin to the body to keep blood sugar levels in the normal range. Symptoms of high blood sugars may include increased thirst and urination, weight loss, blurry vision, hunger, and weakness. If untreated, T1D may rapidly lead to death.

The mainstay for the treatment of T1D is the injection of exogenous insulin. Patients treated with too little insulin will lead to high blood sugars (hyperglycemia) and those treated with too much insulin may exhibit low blood sugars (hypoglycemia). Even with insulin treatment, persons with T1D are at risk for long-term complications of the disease including diabetic retinopathy and macular edema that may lead to blindness, diabetic nephropathy that may lead to kidney failure, diabetic neuropathy that may lead to loss of sensation or pain and puts patients at risk for unrecognized injuries, and vascular disease that may lead to ulcerations, amputations, heart attack, and stroke.

With the discovery of insulin a century ago, the disease was transformed from a rapidly fatal one to a chronic one. T1D is now one of the most common chronic diseases of childhood. However, the fundamental approach of managing the disease with exogenous insulin has not changed for most people with T1D. Better insulin formulations, insulin delivery methods, and monitoring technology have led to improvements in clinical outcomes for many, but the personal and family burden of disease management remains heavy.

Some of the most severely affected individuals with T1D have been eligible to undergo whole pancreas or islet transplants. In some cases, islet transplantation has enabled patients to become insulin independent, free from multiple daily insulin injections and blood glucose monitoring, for longer than 10 years. However, organ donor tissue is scarce and of variable quality; therefore, only limited patients can be treated with this approach. As with most transplants, recipients of these procedures will require lifelong immunosuppression to prevent their immune system from rejecting the transplanted tissue.

Semma scientists have invented a process to produce near limitless numbers of high-quality stem cell-derived islets (SC-islets) starting from human pluripotent stem cells, which are capable of developing (or “differentiating”) into any cell type in the body. This work builds on breakthrough stem cell differentiation technology developed in the laboratory of Professor Doug Melton at Harvard University in 2014 and licensed exclusively to Semma for the generation of cell therapies. Semma’s SC-islets are functionally equivalent to natural islets from a human pancreas, sensing glucose levels and releasing a precise amount of insulin in response. SC-islets from Semma’s clinical manufacturing process are more plentiful, reproducible, and robust than purified human pancreatic islets from organ donors. The SC-islets have been transplanted in both small and large animal models of diabetes where they have been shown to survive for more than half a year, produce physiological levels of human insulin, and safely control glycemia. Beyond the biological advances of creating functional SC-islets in the lab, Semma has successfully scaled this production process in bioreactors to enable large quantities of SC-islets to be produced on a routine basis.