Enzyme Replacement Therapy: A Novel Intervention for Rare Diseases
Roy C. Maynard, M.D., is the Medical Director for PHS. He serves as PHS’s clinical leader, working with the team to provide consultation and advice to ensure quality and effective care to children and their families in their own homes. He also leads implementation of clinical policies, procedures and programs to further enhance the best possible care for each child. He is a Neonatologist and Pediatric Pulmonologist, and served as a staff physician at Children’s Hospitals and Clinics in Minneapolis, Minn for a number of years.
An enzyme is a type of protein that catalyzes chemical reactions in the body. Advances in understanding the human genome has identified enzyme-based defects associated with a myriad of metabolic diseases. The consequence of a faulty gene coding for an enzyme results in a defective enzyme molecule or insufficient quantities of active enzyme – and when this occurs, there is accumulation of a substrate upstream that the enzyme would normally act on. A buildup of substrate (unique to each defect) has destructive effects on cellular and organ function and ultimately manifests as a disease, requiring enzyme replacement therapy.
Manufacturing enzymes for infusion
Lysosomal storage diseases encompass one type of enzyme deficiencies. Lysosomes are intracellular structures that store these enzymes. Advances in molecular biology allow for the manufacturing of a new combination of enzyme to replace the insufficient or defective enzyme that normally reside within the cell. Manufactured recombinant enzymes are modified with increased mannose portions attached to the molecule. After IV infusion, mannose bound enzymes will have a higher affinity to bind to targeted cell’s mannose receptors. This facilitates endocytosis, allowing the enzyme to enter the cell and facilitate reduction of the accumulated toxic substrate.
Enzyme replacement therapy at home
Of the more than 40 identified lysosomal diseases, PHS has provided infusion services for patients with some of these disorders. These include the following diseases;
- Pompe disease
- Gaucher disease
- Fabry disease
- Morquio type A (mucopolysaccharidosis IV)
- Hunter syndrome (mucopolysaccharidosis II)
- Hurler syndrome (Mucopolysaccharidosis type I (MPS I))
For children and their families living with enzyme replacement therapy, this treatment provides hope for improvement of symptoms as well as increased quality and quantity of life. This does come with some hardships including frequent physician visits, costs, laboratory testing, and interruption of day to day routines to incorporate these slowly administered intravenous infusions into their schedules (though this therapy would be an entire day process outside of the home).
Management of reactions
Adverse reactions to enzyme replacement therapy are not uncommon but fortunately usually mild and may be managed with antihistamines and antipyretics as premeds. PHS improves the quality of life for children with these disorders by providing these therapies in a home care setting. Minimizing disruption in the lives of these infants, preschoolers and school age children is all part of taking care of the child.
Originally published: January 17, 2017