Researchers from BioMarin Pharmaceutical, a US biotechnology company, have developed a new technique which they claim could help to reduce patients' immune responses to protein-based drugs.

A number of serious genetic disorders, such as haemophilia A and Pompe disease, can be treated using protein replacement therapies, an increasing number of which are now being developed. Unfortunately, the body's immune system can turn against an introduced protein, significantly affecting the efficacy and safety of such treatments.

The technique developed by BioMarin Pharmaceutical, in conjunction with researchers from the Harbor-University of California involves training the body to tolerate the introduced protein. So far, the researchers have only tested the technique on dogs, but the dog immune system is very similar to that of humans and the researchers are confident that the technique will work on humans.

The technique has two main features: administering the immunosuppressive drugs cyclosporin A and azathioprine, which suppress the production of immune system cells known as T-cells; and using proteins that have a mannose 6-phosphate modification on their N-linked carbohydrates, which ensures that they are speedily taken up by the cells of the body.

When a lysosomal enzyme with the mannose 6-phosphate modification was administered to the dogs on a weekly basis, a 60-day course of cyclosporin A and azathioprine was sufficient to reduce specific antibody levels by a factor of 37 for up to six months.

'These early data provide significant insights into the induction of immune tolerance that are likely applicable to other enzyme replacement therapies and possibly other biopharmaceuticals,' says Emil Kakkis, senior vice president, business operations at BioMarin and one of the lead researchers. 

JE