Moving towards efficient therapies in type 1 diabetes: to combine or not to combine?
Every year, thirty thousand people worldwide are diagnosed with type 1 diabetes mellitus (T1DM). T1DM, also called autoimmune diabetes, is a multifactorial disease affecting predisposed individuals and involving genetic susceptibilities, environmental triggers, as well as unbalanced immune responses. Auto-reactive T cells, produced during the pathogenesis, play an important role by specifically destroying the pancreatic insulin-producing beta-cells in the islets of Langerhans. Numerous therapeutic interventions have been tested, mostly in animal models, but also in humans. To date, only three phase II/III clinical trials have demonstrated safety and efficacy: anti-CD3 antibody, DiaPep277, and GAD65 (in patients with latent autoimmune diabetes in adults). Unfortunately, a significant number of patients did not respond positively and remained insulin-dependent after completion of therapy. Several reasons account for this. Firstly, the severity of the disease as well as the auto-aggressive T cell repertoire vary from patient to patient leading to a broad range of therapeutic efficacies, and secondly at the time of the treatment the number of remaining beta-cells will directly impact the level of insulin production post-treatment. In this review, we will provide some clues to enhance efficacy of future immuno-interventions in patients with T1DM. We suggest that combination therapies might be the best approach.
Bresson
D
D
La Jolla Institute for Allergy and Immunology, Department of Developmental Immunology, San Diego, CA 92121, USA.
von Herrath
M
M
D000818:Animals; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D007114:Immunization; D008954:Models, Biological