Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients

Diabetes Metab Res Rev. 2007 May;23(4):269-75. doi: 10.1002/dmrr.691.

Abstract

Background: Type 1 diabetes results from a T-cell mediated autoimmune destruction of insulin-producing pancreatic beta-cells. The 60-kDa heat-shock protein (hsp60) is one of the known target self-antigens. An immunogenic peptide from hsp60, p277, arrested beta-cell destruction and maintained insulin production in newly diabetic non-obese diabetic (NOD) mice. A randomized, double-blind, phase Ib/II study of peptide treatment was undertaken in recent onset type 1 diabetes patients with remaining insulin production.

Methods: Forty-eight recent onset type 1 diabetes patients were assigned subcutaneous injections of 0.2, 1.0 or 2.5 mg peptide DiaPep277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or four placebo injections (n = 12). The primary clinical endpoints were safety and efficacy (glucagon-stimulated C-peptide production at 6 and 12 months); secondary endpoints were HbA1c levels and daily insulin dose adjusted for body weight at 2, 6, 12 and 18 months.

Results: C-peptide levels decreased over time in all groups except the 2.5 mg-treated. The decrease in C-peptide production was less in treated patients versus placebo, mostly in the 2.5 mg group. HbA1c increased significantly in the 1.0 mg group and in the 2.5 mg group at 2 and 18 months, respectively. No differences were seen in daily insulin doses. One patient was withdrawn from the study possibly owing to a treatment-related adverse event.

Conclusions: Multiple DiaPep277 peptide administration seems safe and may have a beneficial effect on C-peptide levels over time, but this finding is not supported by lower HbA1c levels or daily insulin requirement. Further investigation on a larger scale is warranted.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Peptide / blood*
  • Chaperonin 60
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Insulin / therapeutic use
  • Peptide Fragments
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • C-Peptide
  • Chaperonin 60
  • DiaPep 277
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunologic Factors
  • Insulin
  • Peptide Fragments
  • Peptides