A clinical study led by Linkoping University and financed by pharmaceutical company Diamyd Medical has investigated whether immunotherapy against type 1 diabetes can preserve the body’s own production of insulins. The results suggest that injection of a protein, GAD, into lymph nodes can be effective in a subgroup of individuals. The results have been published in Diabetes Care.
In type 1 diabetes, the body’s immune system attacks the cells that produce insulins when the insulin-producing cells have disappeared, the body can no longer regulate blood sugar level and a person with type 1 diabetes must take exogenous insulin for the rest of his or her life.
A highly topical question in research into type 1 diabetes is whether and if so how, the attack of the immune system can be slowed or completely stopped. One possible strategy is based on altering the immune defence by injecting a protein that the cells of the immune system react to in a form of vaccination. One of the proteins against which the immune system often forms antibodies in type 1 diabetes is known as GAD65 (glutamine acid decarboxylase).
Professor Johnny Ludvigsson at Linkoping University has studied for many years the possibility of vaccinating people who have newly diagnosed type 1 diabetes with GAD. It is hoped that the immune system will become more tolerant against the body’s own GAD, and stop damaging the insulin-producing cells such that the body can continue to form some Insulin.
Studies have shown that even an extremely small production of insulin in the body is highly beneficial for patient health. People with diabetes who produce a certain amount of insulin naturally do not develop low blood sugar levels, hypoglycemia, so easily. They have also a lower risk of developing the life-threatening condition Ketoacidosis which can arise when the insulin level is low “says Johnny Ludvigsson senior professor in the Department of Biomedical and Clinical Science at Linkoping University.
The professor has also led DIAGNODE-2, a clinical phase 2 study in which researchers investigated the effect of GAD- alum(Diamyd) injection into the lymph nodes of 109 young people with recently diagnosed type 1 diabetes.
The natural insulin production of the participants was measured at the start of the study and again after 15 months, several other outcome measures were also followed such as a change in long-term blood sugar levels (HbA1c) and how much supplementary insulin the patients needed to take every day.
Previous studies of immunotherapy in diabetes have suggested that genetic factor play a role in how patients respond to the treatment, this led the researchers in DIAGNOSE-2 to look at several variants of what is known as “HLA genes”. These genes code for protein located on the surface of some cells.
They function as holders of protein and expose them to immune system cells passing by. If the protein fragment exposed in this way comes from, e.g bacteria, the immune system should form antibodies against the foreign protein.
However, the immune system sometimes reacts against the body’s own substance and a certain type of HLA are associated with an increased risk of type 1 diabetes. The HLA variant HLA-DR3-DQ2 exposes the GAD65 protein to cells of the immune system and patient with this variant often form antibodies against GAD65 at an early stage of the disease. Around half of the participants in the study had the HLA-DR3-DQ2 variant.
Treatment with GAD-alum seems to be a promising, simple and safe way to preserve insulin production in around half of patient with type 1 diabetes. The ones who have the right type of HLA. This is why we are looking forward to carrying out larger studies and we hope these will lead to a drug that can change the progress of type 1 diabetes “says Johnny Ludvigsson.
By: Peace Chigozie