A clinical study led by the University of North Carolina medical center indicates that a novel enzyme replacement therapy benefited pediatric patients with Hunter syndrome, a rare genetic disorder for which there are currently no therapeutic treatment options.

The clinical results show that the enzyme replacement therapy can be safely administered and has a favorable impact on a range of clinical problems experienced by patients with Hunter syndrome due to their body's inability to produce the enzyme iduronate-2-sulfatase (I2S). Researchers found that I2S enzyme replacement therapy was associated with significant reductions in liver and spleen volumes, and some patients had reduction in left ventricular hypertrophy, improvements in pulmonary function, and joint mobility.

"Our findings show that -- even at the lowest doses tested -- the enzyme replacement was clinically active and had positive benefits to organ function and physiological measures in several patients in the study," said Joseph Muenzer, of the Department of Pediatrics, Division of Genetics and Metabolism at the University of North Carolina at Chapel Hill who led the study.

In the Phase I/II clinical trial, researchers enrolled 12 patients affected with Hunter syndrome to determine safety of the genetically engineered enzyme and to determine clinical activity. Three dosages of the iduronate-2-sulfatase or I2S protein therapeutic (0.15 mg/kg, 0.5 mg/kg and 1.5 mg/kg) were studied. Within each dose group, patients were randomized to receive either I2S (three patients) or placebo (one patient) by IV infusion biweekly for six months. All twelve patients have successfully completed the six-month study and all elected to enroll in an open-label extension study.

Researchers found that I2S treatment was associated with significant reductions in liver and spleen volumes, improvements in pulmonary function and joint mobility. Infusion-related reactions have occurred in four patients in the middle and high dose groups and have been successfully managed by slowing the infusion rate and using pre-medications. A pivotal multi-centered enzyme replacement clinical trial is expected to begin in 2003.

Hunter syndrome is a genetic disorder, also referred to as mucopolysaccharidosis type II, or MPS II. This hereditary disorder is characterized by the body's inability to produce the enzyme iduronate-2- sulfatase, which is essential in the continuous process of breaking down glycosaminoglycans (complex-carbohydrate containing material present in all body tissues). As a result, glycosaminoglycans remain stored in cells in the body causing progressive damage. The symptoms of Hunter syndrome are not visible at birth, but usually start to become noticeable after the first year of life. Often, the first symptoms may include hernias, frequent ear infections, runny noses, and abnormal facial appearance. As more cells become affected, a variety of symptoms start to appear including enlarged liver and spleen, heart failure, obstructive airway disease, sleep apnea, joint stiffness, and, in the severe form, central nervous system involvement.

The enzyme replacement therapy for Hunter syndrome to replace the relevant enzyme, iduronate-2-sulfatase (I2S), was developed by Transkaryotic Therapies Inc (TKT), a biotechnology company in Cambridge, Massachusetts. Researchers at TKT have determined how to produce large quantities of I2S in genetically-engineered cells, so that I2S can be manufactured outside the body and injected into individuals with Hunter syndrome.