Diabetes vaccine provides promising ends in a genetic subgroup


PICTURE: Johnny Ludvigsson, Senior Professor at Linköping University. view More

Photo credit: Anna Nilsen / Linköping University

A clinical study led by Linköping University and funded by the pharmaceutical company Diamyd Medical examined whether immunotherapy for type 1 diabetes can preserve the body’s own insulin production. The results suggest that injection of a protein, GAD, into lymph nodes may be effective in a subset of individuals. The results were published in Diabetes Care.

In type 1 diabetes, the body’s immune system attacks the cells that produce insulin. When the insulin-producing cells are gone, the body can no longer regulate blood sugar levels, and a person with type 1 diabetes must take exogenous insulin for the rest of their life.

A very topical question in research into type 1 diabetes is whether, and if so, how the attack of the immune system can be slowed down or even stopped completely. One possible strategy is based on changing the immune system by injecting a protein, to which the cells of the immune system react, in the form of a vaccine. One of the proteins that the immune system often makes antibodies to in type 1 diabetes is known as GAD65 (glutamic acid decarboxylase). Professor Johnny Ludvigsson of Linköping University has been researching the possibility of vaccinating GAD in people newly diagnosed with type 1 diabetes for many years. It is to be hoped that the immune system will become more tolerant of the body’s own GAD and will no longer damage the insulin-producing cells, so that the body can continue to produce some insulin.

“Studies have shown that even extremely low levels of insulin production in the body are of great benefit to patient health. People with diabetes who make a certain amount of insulin are less likely to develop low blood sugar and hypoglycemia naturally. They have also a lower risk of developing life-threatening ketoacidosis, which can occur with low insulin levels, “says Johnny Ludvigsson, senior professor at the Institute for Biomedical and Clinical Sciences at Linköping University.

Johnny Ludvigsson led DIAGNODE-2, a phase 2 clinical trial that investigated the effects of GAD alum (Diamyd) injections on the lymph nodes of 109 young people with recently diagnosed type 1 diabetes. The participants’ natural insulin production was measured at the start of the study and again after 15 months. Various other outcome measures were also pursued, such as: B. The change in long-term blood sugar (HbA1c) levels and the amount of extra insulin that patients had to take each day.

Previous studies of immunotherapy for diabetes have shown that genetic factors play a role in how patients respond to treatment. This prompted the researchers in DIAGNODE-2 to examine different variants of the so-called “HLA genes”. These genes code for proteins that are on the surface of some cells. They act as holders of proteins and expose them to passing cells of the immune system. If the protein fragment exposed in this way comes from bacteria, for example, the immune system should produce antibodies against the foreign protein. However, the immune system is sometimes responsive to the body’s own substances, and certain types of HLA are linked to an increased risk of type 1 diabetes. The HLA variant HLA-DR3-DQ2 exposes the GAD65 protein to cells of the immune system, and patients with this variant often develop antibodies to GAD65 at an early stage of the disease. About half of the study participants had the HLA-DR3-DQ2 variant.

For the entire patient population, there was no difference between treatment and placebo in the extent to which insulin production was maintained. However, GAD alum had a positive effect on the subgroup of patients who had the DR3-DQ2 variant of the HLA genes.

“The patients in the subgroup with the HLA genes of the DR3-DQ2 type did not lose insulin production as quickly as the other patients. In contrast, we could not find any significant effect in the patients who did not have this HLA type.” says Johnny Ludvigsson.

No adverse effects that might be related to treatment with GAD alum were observed during the study.

“Treatment with GAD alum appears to be a promising, easier, and safer way to maintain insulin production in about half of patients with type 1 diabetes who have the right type of HLA, so we look forward to them Conduct larger studies, and we hope these will result in a drug that can alter the progression of type 1 diabetes, “says Johnny Ludvigsson.

The study was funded by Diamyd Medical AB, the Swedish Children’s Diabetes Foundation and the Swedish Diabetes Foundation. The pharmaceutical company Diamyd Medical was involved in the planning and data collection. One of the authors, Ulf Hannelius, is employed by Diamyd Medical.

The study:

The 109 participants, aged between 12 and 24 years, had been diagnosed with type 1 diabetes in the past 6 months and were randomly assigned to one of two groups. One group received three injections of GAD alum at 1 month intervals and vitamin D in tablet form, while the other group (controls) received placebo. Neither the participants nor the researchers knew which patients were being treated with GAD alum (the study was randomized and double-blind).

The article: “Intralymphatic glutamic acid decarboxylase with vitamin D supplementation in recent type 1 diabetes: a double-blind, randomized, placebo-controlled phase IIb study”, Johnny Ludvigsson, Zdenek Sumnik, Terezie Pelikanova, Lia Nattero Chavez, Elena Lundberg, Itxaso Rica Maria A. Martínez-Brocca, Mari Sol Ruiz de Adana, Jeanette Wahlberg, Anastasia Katsarou, Ragnar Hanas, Cristina Hernandez, Maria Clemente León, Ana Gómez-Gila, Marcus Lind, Marta Ferrer Lozano, Theo Sas, Ulf Samuelsson , Stepanka Pruhova, Fabricia Dietrich, Sara Puente Marin, Anders Nordlund, Ulf Hannelius and Rosaura Casas, (2021), Diabetes Care, published online on May 21, 2021, doi: 10.2337 / dc21-0318


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