The Diamyd
® portfolio is based on the 65 kDa isoform of the recombinant human glutamic acid decarboxylase protein, isoform 65 kDa (rhGAD65). Endogenous GAD65 is present in insulin-producing beta cells as well as in nerve and brain tissues. Though its role in beta cells is not fully understood, GAD65 catalyzes the conversion of the amino acid glutamate to GABA, a neurotransmitter, in nerve cells. GAD65 is considered an important candidate drug in several neurological diseases, including Parkinson's disease and chronic pain.
GAD65 is also a major autoantigen in autoimmune diabetes. Diamyd
® is intended to induce immunotolerization in patients with autoimmune diabetes to slow or prevent the destruction of pancreatic beta cells and to maintain endogenous secretion of insulin.
Type 1 diabetes and LADA (Latent Autoimmune Diabetes in Adults) patients are the primary populations that might benefit from Diamyd
® therapy. Both diseases are autoimmune in nature, which means that the body's immune system attacks its own insulin producing beta cells.
DIAMYD® DIABETES VACCINE
The therapeutic diabetes vaccine Diamyd
® has shown clinical trial efficacy in preserving beta cell function in patients with type 1 diabetes and in LADA patients. No serious adverse events related to Diamyd
® treatment have been reported in any study. In type 1 diabetes and LADA, where the immune system attacks the body's own insulin secreting cells, administration of Diamyd
® can arrest or slow down the disease process. This allows the patients to maintain their own insulin secretion, which in turn leads to improved metabolic control and reduced hypoglycemic risk and reduces long-term diabetes complications. Furthermore, it may allow for regeneration of beta cells in a non-autoimmune environment, thus setting the stage for a cure of the disease. It is also possible that the treatment can prevent type 1 diabetes in patients at high risk of developing the disease. Diamyd
® is developed in two separate formulations, one for LADA, which is in Phase II of clinical development, and one for type 1 diabetes, currently in Phase III clinical trials in both US and Europe.
Read more about the Diamyd® vaccines here.
DIAMYD® MECHANISM OF ACTION
Studies in preclinical models for autoimmune diabetes and results from clinical trials have demonstrated that the destruction of the beta cells in autoimmune diabetes is mediated by the cellular arm of the immune system involving antigen-specific killer T-cells. The antibody arm of the immune system, the humoral arm, has more of a bystander role and is not actively involved in the destructive process.
Several findings point to a mechanism of action where the subcutaneous deposit of rhGAD65 is processed by antigen-presenting cells to provide peptide fragments of rhGAD65 containing regions (determinants) recognized by T-cells. Presentation of those rhGAD65 determinants with tolerizing potential results in induction and proliferation of a subset of GAD65-specific regulatory T-cells. These regulatory T-cells down regulate antigen-specific killer T-cells that would otherwise attack the insulin secreting beta cells. Thus, the proliferation of GAD65-specific regulatory T-cells results in either an inhibition or prevention of the autoimmune disease process.