Myozyme (alglucosidase alfa) is a medication for a rare genetic disorder. It functions as an enzyme replacement therapy, providing a missing protein to the body. This therapy manages the underlying cause by supplementing the deficient enzyme. Myozyme represents a significant advancement in treating this condition.
Understanding Pompe Disease
Pompe disease is a rare, inherited neuromuscular disorder characterized by progressive muscle weakness. Also known as glycogen storage disease type II or acid maltase deficiency, the genetic cause is a mutation within the GAA gene, which produces the enzyme acid alpha-glucosidase (GAA).
A deficiency of the GAA enzyme prevents the breakdown of glycogen, a complex sugar, within cells. Glycogen then accumulates in lysosomes, cellular compartments responsible for waste breakdown. This buildup predominantly affects muscle cells, including those in the heart, diaphragm, and skeletal muscles, impairing their normal function.
There are two primary forms of Pompe disease: infantile-onset and late-onset. Infantile-onset Pompe disease typically manifests within the first few months after birth, presenting with severe symptoms such as generalized muscle weakness, poor muscle tone, feeding difficulties, and an enlarged heart. Infants often experience respiratory distress and may fail to thrive.
The late-onset form can appear later in childhood, adolescence, or adulthood. Symptoms include progressive muscle weakness, particularly in the limbs and trunk, muscle cramping, and fatigue. Respiratory difficulties are common. While cardiac involvement is less frequent than in the infantile form, it can still occur.
Myozyme’s Mechanism of Action and Administration
Myozyme provides a functional acid alpha-glucosidase (GAA) enzyme. This medication is an enzyme replacement therapy (ERT), introducing an exogenous enzyme to compensate for the body’s deficiency. Alglucosidase alfa, the active substance in Myozyme, is a recombinant form of human GAA, produced using recombinant DNA technology.
Once administered, this replacement enzyme targets lysosomes within cells, where it helps to break down the accumulated glycogen. Myozyme prevents further harmful buildup and helps to reduce existing glycogen deposits. This action can stabilize or restore the function of affected cardiac, skeletal, and respiratory muscles.
Myozyme is administered via intravenous (IV) infusion. The medication comes as a powder that is reconstituted with sterile water and then diluted with a sodium chloride solution before infusion. A typical dosage is 20 mg per kilogram of body weight every two weeks.
The infusion process begins slowly at 1 mg/kg/hour, gradually increased by 2 mg/kg/hour every 30 minutes, provided there are no signs of adverse reactions, until a maximum rate of 7 mg/kg/hour is reached. This incremental approach allows for careful monitoring of patient tolerance. Myozyme infusions are typically performed in a hospital or specialized infusion center under the supervision of a physician.
Managing Treatment and Potential Reactions
Ongoing management of Myozyme treatment involves regular monitoring by healthcare professionals to assess its effectiveness and the patient’s response. This includes evaluating clinical manifestations of the disease and checking for IgG antibodies, especially within the first two years of treatment and then annually. High and sustained IgG antibody titers may reduce the effectiveness of the therapy.
Infusion-associated reactions (IARs) are common during Myozyme administration, with approximately 39% of patients experiencing them. Reactions can range from mild symptoms like flushing, rash, fever, and itching to more severe manifestations such as urticaria, tachycardia, decreased oxygen saturation, and bronchospasm. Severe reactions, including anaphylaxis, can occur during or up to three hours after the infusion, and some have been life-threatening.
Management of IARs involves slowing the infusion rate, temporarily stopping the infusion, and administering pre-medications such as antihistamines, antipyretics, or corticosteroids. For severe allergic reactions, immediate discontinuation of the infusion and emergency medical interventions, including epinephrine, may be necessary. Patients with advanced Pompe disease or compromised cardiac and respiratory function may face an increased risk of severe complications from IARs, necessitating close monitoring during infusions.