Prenatal Enzyme Therapy Could Help Treat Rare Genetic Disease

The first test of in-utero enzyme replacement therapy (ERT) proved safe and effective for a baby with infantile-onset Pompe disease, according to a recent case report in the New England Journal of Medicine.

An infant with cross-reactive immunologic material (CRIM)-negative infantile-onset Pompe disease, which is the most severe end of the disease spectrum, had no cardiac manifestations following treatment, compared to her two affected siblings who had cardiomyopathies and died early in life.

Related Article: Sanofi’s New Pompe Disease Treatment Wins Approval in Europe 

Finding Creative Solutions to Treat Pompe Disease

Pompe disease is a rare inherited disease, with an estimated one in every 40,000 births. It only occurs when both parents carry a defective gene for an enzyme that breaks down glycogen. The flawed gene results in low levels of acid alpha-glucosidase (GAA), which allows glycogen to build up in muscle and cardiac cells, causing an enlarged heart and muscle weakness. 

Since 2006, the outlook for kids with Pompe disease has improved thanks to enzyme replacement therapy, which delivers infusions of a synthetic version of GAA every week or two starting at birth or after doctors discover the disease. However, there is no GAA available for the infantile-onset subtype, which the current patient faces, and heart damage begins in-utero. Patients usually develop hypertrophic cardiomyopathy prenatally and hypertonia at birth and, left untreated, typically die by age of two. 

Administering Treatment In Utero for Various Lysosomal Storage Diseases

To solve the problem from the very beginning of life, scientists came up with the idea of delivering an enzyme into the womb before birth. Providing the enzyme to a fetus might train its still-developing immune system to accept the synthetic protein rather than make antibodies that block it, as babies receiving GAA after birth often do. In addition, the enzyme should also reach the brain more readily, as the blood-brain barrier is not fully formed early in fetal development.

In the same clinical trials, the researchers will subsequently try the in-utero strategy on eight different lysosomal storage diseases, and they have already administered enzymes to two more fetuses. All participants must be closely followed after birth as the blood-brain barrier closes as children age, and the enzyme therapy will eventually stop reaching their brains, which could lead to damage.  

As the current results suggest that moving the window for therapeutic intervention into the prenatal period may further improve postnatal outcomes, researchers expect to start treatment as early as possible. They hope that the in-utero treatment will delay the onset of those problems until the children become eligible for treatments that could be permanent, such as stem cell transplants or gene therapies in clinical trials.

Author

Nai Ye Yeat