Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients.
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 One patient was withdrawn from the study possibly owing to a treatment-related adverse event.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.
Huurman
Volkert A L
VA
Department of Immunohematology and Blood transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Decochez
Katelijn
K
Mathieu
Chantal
C
Cohen
Irun R
IR
Roep
Bart O
BO
D002096:C-Peptide / Q000097:blood*; D018834:Chaperonin 60; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D010446:Peptide Fragments; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D002096:C-Peptide; D018834:Chaperonin 60; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C447781:DiaPep 277