A medical examine led by Linköping College and financed by prescription drugs firm Diamyd Medical has investigated whether or not immunotherapy in opposition to sort 1 diabetes can protect the physique’s personal manufacturing of insulin. The outcomes counsel that injection of a protein, GAD, into lymph nodes will be efficient in a subgroup of people. The outcomes have been printed in Diabetes Care.
In sort 1 diabetes, the physique’s immune system assaults the cells that produce insulin. When the insulin-producing cells have disappeared, the physique can not regulate blood sugar degree, and an individual with sort 1 diabetes should take exogenous insulin for the remainder of his or her life.
A extremely topical query in analysis into sort 1 diabetes is whether or not, and if that’s the case how, the assault of the immune system will be slowed and even fully stopped. One attainable technique relies on altering the immune defence by injecting a protein that the cells of the immune system react to, in a type of vaccination. One of many proteins in opposition to which the immune system usually varieties antibodies in sort 1 diabetes is named GAD65 (glutamic acid decarboxylase). Professor Johnny Ludvigsson at Linköping College has studied for a few years the opportunity of vaccinating individuals who have newly recognized sort 1 diabetes with GAD. It’s hoped that the immune system will change into extra tolerant in opposition to the physique’s personal GAD, and cease damaging the insulin-producing cells, such that the physique can proceed to type some insulin.
“Research have proven that even an especially small manufacturing of insulin within the physique is very helpful for affected person well being. Individuals with diabetes who produce a certain quantity of insulin naturally don’t develop low blood sugar ranges, hypoglycaemia, so simply. They’ve additionally a decrease threat of creating the life-threatening situation ketoacidosis, which may come up when the insulin degree is low”, says Johnny Ludvigsson, senior professor within the Division of Biomedical and Scientific Sciences at Linköping College.
Johnny Ludvigsson has led DIAGNODE-2, a medical section 2 examine by which researchers investigated the impact of GAD-alum (Diamyd) injections into the lymph nodes of 109 younger folks with not too long ago recognized sort 1 diabetes. The pure insulin manufacturing of the members was measured firstly of the examine and once more after 15 months. A number of different end result measures had been additionally adopted, corresponding to change in long-term blood sugar ranges (HbA1c), and the way a lot supplementary insulin the sufferers wanted to take daily.
Earlier research of immunotherapy in diabetes have instructed that genetic components play a task in how sufferers reply to the therapy. This led the researchers in DIAGNODE-2 to have a look at a number of variants of what are referred to as “HLA genes.” These genes code for proteins positioned on the floor of some cells. They perform as holders of proteins, and expose them to immune system cells passing by. If the protein fragment uncovered on this method comes from, for instance, micro organism, the immune system ought to type antibodies in opposition to the overseas protein. Nonetheless, the immune system typically reacts in opposition to the physique’s personal substances, and sure kinds of HLA are related to an elevated threat of sort 1 diabetes. The HLA variant HLA-DR3-DQ2 exposes the GAD65 protein to cells of the immune system, and sufferers with this variant usually type antibodies in opposition to GAD65 at an early stage of the illness. Round half of the members within the examine had the HLA-DR3-DQ2 variant.
For the whole affected person group, there was no distinction between therapy and placebo within the diploma to which insulin manufacturing was preserved. GAD-alum did, nevertheless, have a constructive impact for the subgroup of sufferers who had the DR3-DQ2 variant of HLA genes.
“The sufferers within the subgroup with the DR3-DQ2 sort of HLA genes didn’t lose insulin manufacturing as shortly as the opposite sufferers. In distinction, we didn’t see any important impact within the sufferers who didn’t have this HLA sort”, says Johnny Ludvigsson.
No undesired results that may very well be associated to therapy with GAD-alum had been seen through the examine.
“Therapy with GAD-alum appears to be a promising, easy and secure option to protect insulin manufacturing in round half of sufferers with sort 1 diabetes, those who’ve the precise sort of HLA. Because of this we’re trying ahead to finishing up bigger research, and we hope these will result in a drug that may change the progress of sort 1 diabetes”, says Johnny Ludvigsson.
The examine has been financed by Diamyd Medical AB, the Swedish Little one Diabetes Basis, and the Swedish Diabetes Basis. The pharmaceutical firm Diamyd Medical was concerned in planning and the gathering of information. One of many authors, Ulf Hannelius, is employed by Diamyd Medical.
The 109 members, aged between 12 and 24 years, had been recognized with sort 1 diabetes inside the previous 6 months, and had been allotted at random to one among two teams. One group acquired three injections of GAD-alum at intervals of 1 month and vitamin D in pill type, whereas the opposite group (controls) acquired placebo. Neither the members nor the researchers knew which sufferers acquired therapy with GAD-alum (the examine was randomized and double-blind).
Reference: “Intralymphatic glutamic acid decarboxylase with Vitamin D supplementation in latest onset Kind 1 diabetes: a double-blind randomized placebo-controlled Part IIb trial” by Johnny Ludvigsson, Zdenek Sumnik, Terezie Pelikanova, Lia Nattero Chavez, Elena Lundberg, Itxaso Rica, Maria A Martínez-Brocca, MariSol 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, 21 Could 2021, Diabetes Care.