Vertex – type 1 diabetes vs stem cell therapy

Diabetes mellitus (DM) is a chronic metabolic disorder defined by insufficient secretion of insulin or insulin resistance. There are four major types of DM: type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes, and monogenic diabetes. 

Type 1 diabetes (also known as insulin dependent DM) is characterised by the autoimmune destruction of pancreatic β-cells. This destruction of β-cells results in a lack of production of insulin. Insulin is crucial to maintain healthy levels of glucose in the blood. The cause of this autoimmunity is not completely understood, but chronic hyperglycaemia (high blood glucose) can cause damage to blood vessels and nerves. If left untreated, hyperglycaemia can result in death.

In the UK, approximately 400,000 people are currently living with type 1 diabetes. In fact, the UK has one of the highest rates of type 1 diabetes in the world, for reasons that are currently unknown. Treatment for these individuals is traditionally via regular insulin injections to maintain normal blood sugar levels. Individuals with type 1 diabetes will have around 65,000 injections and measure their blood glucose more than 80,000 times in their lifetime.

Stem cell therapy […] utilises the potentiality of stem cells to differentiate into any cell type, in this case pancreatic β-cells

To improve the quality of life of individuals with type 1 DM, there has been a wide range of treatment options explored. For example, clinical pancreas or islet transplantation has been considered a feasible treatment option. The first pancreas transplant was conducted by Dr Richard Lillehei in 1966, and up until 2015, more than 50,000 patients worldwide had received pancreas transplants according to the International Pancreas Transplant Registry. However, the worldwide shortage of pancreas donors and immune rejection has proved to be a major challenge to islet transplantation.  Consequently, scientists have begun focusing on stem cell therapy as a method of treating type 1 DM. 

Stem cell therapy is a form of regenerative medicine designed to repair damaged cells within the body. This form of medicine utilises the potentiality of stem cells to differentiate into any cell type, in this case pancreatic β-cells. Embryonic stem cells (cells taken from an early mammalian embryo) are known as pluripotent cells. Pluripotency means that these cells have the ability to proliferate indefinitely, self-renew, and the capacity to differentiate into multiple types of adult cells. If scientists can place these embryonic stem cells under specific biological conditions, these stem cells can differentiate into pancreatic β-cells. 

The creation of VX-880 (an investigational stem cell derived therapy for pancreatic β-cells) can be traced back to Dr Doug Melton, a stem-cell biologist at Harvard University in Cambridge, Massachusetts. He was a developmental neurobiologist until his six-month-old son was diagnosed with type 1 DM in the early 1990s. He then vowed to find a cure for the condition, leading to his entrance into the stem-cell field. 15 years later, Melton and his stem cell lab were able to successfully convert stem cells into islet cells. Melton’s group published their methods in 2014. In 2015, Melton co-founded a start-up company which was acquired by Vertex in Boston, Massachusetts for US$950 million in September 2019. 

The success of VX-880 in this singular patient has the potential to transform not only the lives of individuals with type 1 DM, but also the economic landscape of the disease

This method of treatment is currently undergoing clinical trials with Vertex Pharmaceuticals. Recently, Vertex announced that the first type 1 DM patient to be dosed with VX-880 saw their need for insulin disappear almost entirely. The patient was initially injected with a single infusion of the synthetic pancreatic β-cells, and after 90 days was able to produce a steady flow of insulin and maintain insulin production after eating. The patient, Brian Shelton, told the New York Times that his treatment is “like a miracle” and it has given him a “whole new life”. 

This is the first demonstration of a patient with type 1 DM achieving restored islet cell function from such a therapy. Vertex plans to enrol approximately 17 other participants for their early-stage trial. In its current form, VX-880 requires recipients to go on life-long immunosuppressants, therefore the therapy’s risk to benefit ratio may only be viable for those with the severest form of the disease. However, the success of VX-880 in this singular patient has the potential to transform not only the lives of individuals with type 1 DM, but also the economic landscape of the disease. Economically, this would transform those suffering with type 1 diabetes as it would be a one-time functional cure that could revolutionise the lives of these people. 

As Brain Shelton said, this treatment could provide a new life for these patients. Type 1 diabetes can be an extremely debilitating disease that requires consistent monitoring and treatment. With VX-880, millions of people around the world could soon be free from insulin injections and glucose level monitoring, much like a miracle.