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Hearts shrank to normal in 12 weeks
Hearts back to normal
Megan and Patrick had only months to live by the time the medicine reached them, and the enlarged heart was what would have killed them in that window. The medicine was the enzyme replacement therapy their disease required, built by a company their father had started to make it.
The plateau
For the first six to nine months, their muscle strength improved, particularly Megan's. At about a year it began to plateau, and the steady decline of the disease continued. The medicine had saved their lives and the lives of others with Pompe disease, but it wasn't a cure and it wasn't the best treatment that could be developed.
A second company
John Crowley had thought of his work in biotech as an 18-month foray and planned to do something else afterward. The plateau changed that. He looked at a lot of technologies and decided the next company had to be a marathon after the first one's all-out sprint: a long journey to develop a next-generation Pompe medicine. That company became Amicus.
How does enzyme therapy shrink an enlarged heart?
In Pompe disease the heart muscle swells with stored glycogen, which thickens its walls. Enzyme replacement supplies the missing enzyme, which breaks the glycogen down inside the cells. As the stored material clears, the wall thickness falls. Trials of alglucosidase alfa in infants, reported in the journal Neurology in 2007, found improved survival and a drop in the size of the heart's left ventricle.
Why does the benefit fade after a year?
Researchers have pointed to several factors in long-term follow-up of treated patients. The enzyme enters skeletal muscle cells less efficiently than it enters other tissue, and muscle damaged before treatment may not fully recover. Patients who make no working version of the enzyme at all are especially likely to form antibodies against the drug, a status known as CRIM-negative.
How are newer Pompe drugs different?
Enzyme drugs reach muscle by binding to receptors that recognize a sugar tag called mannose-6-phosphate, and the older enzyme carried few of these tags. Newer enzymes were engineered with more of them, so more of each dose is taken up by muscle. One newer therapy pairs such an enzyme with miglustat, a small molecule that keeps the enzyme stable in the blood. The US FDA approved that combination, cipaglucosidase alfa with miglustat, in 2023.
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