Immune modulation in type 1 diabetes mellitus using DiaPep277: a short review and update of recent clinical trial results.
In type 1 diabetes mellitus, autoimmune T-cells mount an attack on insulin producing beta-cells eventually causing hyperglycemia. It is hypothesized, that to prevent and treat this disease, one must interfere with the autoimmune process. To avoid hazardous side effects, this intervention should not cause a global immune suppression but immune modulation. DiaPep277 (peptide 277) is a 24 amino acid peptide derived from positions 437-460 in HSP60. It has recently been shown to have an immune modulatory effect on diabetogenic T cells in animal models of diabetes. It has also been recently implicated as a possible auto-antigen in type 1 diabetes. Promising results in animal models led to phase 1 to 3 human clinical trials in patients with type 1 diabetes, the results of which are the focus of this review. A combined analysis of all the adult phase II studies revealed that DiaPep277 significantly inhibits the decline in stimulated C-peptide secretion (thus preserving endogenous insulin secretion). This effect was more pronounced in patients with a high beta-cell reserve at the start of the treatment. Furthermore, opposite trends in glycemic control of DiaPep277 treated patients where noted as opposed to placebo treated patients. The phase III study has began more than 2 years ago in 40 medical centers worldwide, and thus far recruited over 350 patients around the world. If DiaPep277 will prove to be efficacious, it will cause a paradigm shift in the treatment of type 1 diabetes, from treating the subsequent insulin deficiency to addressing the initial autoimmune process that is at the heart of the disease.
Eldor
Roy
R
Diabetes Research Center, Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel. eldorroy@yahoo.com
Kassem
Sameer
S
Raz
Itamar
I
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000187:drug effects / Q000378:metabolism; D018834:Chaperonin 60 / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
D001786:Blood Glucose; D002096:C-Peptide; D018834:Chaperonin 60; C447781:DiaPep 277; D007155:Immunologic Factors; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides