Protection of neuronal cell death against diabetes-induced apoptosis by Fas blocker ZB4

Objective: To determine the role of apoptosis inhibition in the prevention of diabetic neuropathy using the antiFas cell surface death receptor (Fas) antagonistic monoclonal antibody ZB4. Methods: This prospective study enrolled patients with type 2 diabetes with and without neuropathy and a group of healthy controls. The serum concentrations of Fas and Fas ligand (FasL) were measured in all study participants using an enzyme-linked immunosorbent assay. The ability of serum from study participants to induce apoptosis was evaluated in a human neuronal cell line using flow cytometry. Results: A total of 28 healthy subjects and 57 patients with diabetes were enrolled in the study. Serum Fas concentrations were significantly increased in diabetes patients with and without neuropathy compared with the controls. Cells treated with the serum from diabetes patients with neuropathy had significantly higher rates of early apoptosis compared with cells treated with control serum. Monoclonal antibody ZB4 was able to block serum-induced apoptosis. Conclusions: Serum-induced apoptosis of a human neuronal cell line appeared to be mediated via Fas, which suggests that targeting and inhibiting Fas might offer a therapeutic target for diabetic neuropathy.