Nov. 20, 2008

Effectiveness of Pompe Enzyme Replacement Varies

Two children and one adult with Pompe disease (also called acid maltase deficiency who’ve been receiving long-term acid maltase enzyme replacement therapy have stabilized or improved, say researchers in the Netherlands, who published their findings in June in Neuromuscular Disorders.

Ans van der Ploeg at Erasmus University Medical Center-Sophia Children’s Hospital in Rotterdam, the Netherlands, and colleagues followed three patients with Pompe disease for eight years.

For the first three years, the patients received acid maltase enzyme from rabbits. After that, they began receiving a laboratory-formulated acid maltase product now known as Myozyme. The compound, which is made in cells, received approval from the U.S. Food and Drug Administration in 2006.

Myozyme has to be infused intravenously. By the time of study publication, the three patients had each received about 380 infusions over eight years of treatment. All have now reached adulthood.

The first patient, who was 16 when she began treatment and whose skeletal and pulmonary muscle function had declined rapidly in four years, experienced a stabilization of her pulmonary function in the first three years of the study, with fewer hours of mechanical ventilation required. She also experienced a slight increase in other muscle function.

Over the next five years, her pulmonary function and the number of hours of ventilation she required remained stable, and her strength increased in several skeletal muscle groups. As her functioning improved, she resumed her education and started law school in 2007.

The second patient, 32 when he started enzyme treatment, had lost almost all voluntary muscle movement and was completely dependent on invasive ventilation. He was in bed 21 hours per day.

During the first three years of treatment, his respiratory function stabilized, his total muscle strength improved slightly, and he began staying up 13 hours a day.

Over the next five years, his strength and muscle function stabilized, as did his respiratory status, although he continued to require ventilation. He became able to perform domestic and leisure activities, and his quality of life improved.

The third patient, who was 11 when he started treatment, had normal pulmonary function and could bear some weight, although he had been using a wheelchair for two years.

Over the first three years of treatment, he experienced an enormous improvement in muscle strength and function, and over the next five years, his strength reached normal values for all muscle groups. His pulmonary function also normalized, he became able to participate in sports and other activities, and he began working as a gardener.

“Obviously, our limited observations cannot be taken as proof that enzyme therapy exerts long-term beneficial effects in children and adults with Pompe disease,” the authors note, “but they provide an important guideline for the broader application of enzyme replacement therapy. ... Our report indicates that follow-up should be continued for several years to assess the full effect of therapy.”

In an unrelated article, published in the July 29 issue of Neurology, Joe Brierley at Great Ormond Street Hospital in London and colleagues raise the question of the value of enzyme replacement therapy in infants with severe Pompe disease who are dependent on assisted ventilation or are on the verge of becoming so. They cite two cases in which such therapy did not prevent death and may have prolonged the babies' distress.