A tolerant alternative to immunosuppression

Two research teams have shown that temporary monotherapy with human a₁-antitrypsin can lead to long-term protection against inflammation-mediated and T cell-mediated destruction of islet b-cells in mice. The results, which were achieved without the use of immunosuppressants, could bolster the prospects for islet transplantation in patients with type 1 diabetes by overcoming two of the main drawbacks associated with such therapy: immunosuppressant use and eventual loss of graft function.

Both groups are already planning clinical trials to evaluate AAT in type 1 diabetics.

Human a₁-antitrypsin (SERPINA1; AAT) is an anti-inflammatory serine protease inhibitor that is marketed as an enzyme replacement therapy for patients with a defective version of the protein (AAT deficiency). The Baxter International Inc., Prolastin from Talecris Biotherapeutics Inc. and Zemaira from the CSL Behring unit of CSL Ltd.

In a paper published in the Proceedings of the National Academy of Sciences, researchers at the University of Colorado Health Sciences Center and Ben-Gurion University of the Negev showed that AAT monotherapy resulted in dose-dependent increases in acceptance rates of allogeneic islet b-cell grafts and normal glucose levels in diabetic mice.¹ The