Overview
Mucopolysaccharidosis type I (MPS I), Hurler-Scheie syndrome, Hurler syndrome, and Scheie syndrome are lysosomal storage disorders (LSD). A deficiency in the lysosomal enzyme alpha-L-iduronidase results in the disease. Mucopolysaccharidosis type I patients can have diverse clinical spectrums, ranging from classical Hurler syndrome to attenuated Scheie syndrome. Enzyme replacement therapy with Laronidase has been developed as a treatment modality for MPS I patients. It has been approved for clinical practice as the intravenous Laronidase therapy is well tolerated and effective for treating MPS I patients without neuronal pathology. Recent challenges for treatment for MPS I patients include methods to predict disease severity, developing an early screening protocol that identifies patients before the onset of irreversible pathology, appropriate treatment for neuropathology, and an effective patient monitoring system.
How Does Laronidase Work?
Laronidase is a precise recombinant alpha-L-iduronidase and is a Food and Drugs Administration (FDA) approved drug for the long‐term treatment of MPS I. It is created by recombinant DNA (deoxyribonucleic acid) technology in a Chinese hamster ovary cell line. The cause of treatment is to provide exogenous enzymes for uptake into lysosomes, and so to increase the catabolism of GAGs (glycosaminoglycans) and prevent their build-up in tissues. The mannose‐6‐phosphateterminated oligosaccharide chains of Laronidase bind to specific mannose‐6‐phosphate receptors. This pathway mediates the uptake of lysosomes. Patients develop antibodies by week 12 of the drug administration. Therefore these patients are routinely pre‐medicated with antihistamines and antipyretics one hour before the drug administration.
Uses:
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Mucopolysaccharidosis (MPS) Type 1- Laronidase is a form of recombinant human alpha-L-iduronidase, which is a medication used to treat two forms of Mucopolysaccharidosis I (MPS I), which is also known as Hurler syndrome. These two forms are the Hurler form and the Hurler-Scheie form. Both forms are caused by a genetic deficiency of the enzyme alpha-L-iduronidase, which leads to the accumulation of glycosaminoglycans (GAGs) in various tissues and organs of the body. Laronidase works by breaking down these GAGs, which can help to reduce the symptoms and slow the progression of the disease.
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Other Uses- Laronidase is a medication that is only approved and used to treat Mucopolysaccharidosis I (MPS I), also known as Hurler syndrome and Hurler-Scheie forms, which is caused by a deficiency of the enzyme alpha-L-iduronidase. Therefore, it is not used for any other indication.
Dosage:
The recommended dosage for Laronidase is 0.58 mg/kg. It is administered every week as an intravenous infusion.1 ml of the drug contains 100 units (approximately 0.58 mg) of Laronidase. It is a recombinant form of human alpha-L-iduronidase and is produced by recombinant DNA (deoxyribonucleic acid) technology and cell culture.
Warning:
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Sudden vision loss, tunnel vision, blurred vision, seeing halos around lights, or eye pain may be symptoms of serious eye complications. It should be reported to a doctor immediately.
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Symptoms such as irregular, or fast heartbeats, shortness of breath, fluttering in the chest, lightheadedness, or sudden dizziness may indicate heart problems and should be immediately evaluated by a doctor.
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Severe headache, slurred speech, confusion, arm or leg weakness, loss of coordination, trouble walking, feeling unsteady, high fever, very stiff muscles, profuse sweating, or tremors may be symptoms of serious neurological complications and should be reported to a doctor immediately.
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It is essential to contact a healthcare professional if these symptoms are experienced during or after treatment with Laronidase.
For Patients:
Learn About Mucopolysaccharidosis Type I (MPS I)
What Is Mucopolysaccharidosis Type I (MPS I)?
MPS I, also known as Hurler syndrome, is a rare genetic disorder that affects many parts of the body, including the bones, joints, heart, lungs, and nervous system. A deficiency of the enzyme alpha-L-iduronidase causes it. As a result of this deficiency, these molecules build up in various tissues and organs, leading to a wide range of symptoms and health problems. Other types of MPSs include MPS II (Hunter syndrome), MPS III (Sanfilippo syndrome), and MPS IV (Morquio syndrome), each caused by a deficiency of a different enzyme.
Causes:
MPS I (Mucopolysaccharidosis type I) is a genetic disorder caused by a deficiency of the enzyme lysosomal alpha-L-iduronidase, which is responsible for breaking down long chains of sugar molecules called glycosaminoglycans. This means that the affected person inherits genes, to develop the disease. Symptoms of MPS I can range from mild to severe, depending on the amount of enzyme activity present. The mild form of the disorder, called attenuated MPS I, is characterized by less severe symptoms and a later onset, while the severe form, called severe MPS I, is characterized by more severe symptoms and an earlier onset. Symptoms can include developmental delays, joint stiffness, an enlarged liver and spleen, a distinctive facial appearance, and heart problems.
Alternative Names:
Alpha-L-iduronate deficiency, severe MPS I, mucopolysaccharidosis type I, attenuated MPS I, MPS I S, MPS I H, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, MPS 1 H/S, lysosomal storage disease - mucopolysaccharidosis type I.
Before Starting Laronidase:
How Effective Is Laronidase for Mucopolysaccharidosis Type I (MPS I)?
Laronidase is a medication that has been shown to be effective in treating Mucopolysaccharidosis type I (MPS I), a rare genetic disorder that affects the breakdown and removal of certain sugars in the body. In clinical trials, Laronidase has been shown to improve breathing, walking, and joint mobility, as well as reduce the size of the liver and spleen. It also improves the overall quality of life and prolongs survival in patients with MPS I. The treatment should be started as soon as the diagnosis is confirmed to prevent or slow down the progression of the disease. The effectiveness of the treatment will depend on the individual case, and it is important to work closely with a healthcare provider to monitor progress and adjust the treatment as needed.
Things to Tell Physicians Before They Prescribe Laronidase for Mucopolysaccharidosis Type I (MPS I):
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Laronidase is a medication used to treat a rare genetic disorder called Mucopolysaccharidosis type I (MPS I).
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If there is an allergy to Laronidase, the patient should not use this medication. The patient’s infusion may be delayed if they have a fever or cold symptoms.
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Before using Laronidase, inform the concerned doctor if there are any breathing problems, heart disease, or sleep apnea.
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Inform the doctor about are pregnant or breastfeeding, as it is not known if Laronidase will harm an unborn baby.
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The patient may need to be listed on an MPS I registry while using this medicine to track the disorder's progression and the long-term effects of Laronidase on treatment.
Starting Laronidase for Mucopolysaccharidosis Type I (MPS I)-
How to Take Laronidase?
Laronidase is typically administered by intravenous (IV) infusion, which means it is given directly into the bloodstream through a vein. The infusion is typically given once a week. The dosage and the required time of the treatment will depend on the individual case and the severity of the disorder. The healthcare provider will determine the appropriate dosage and schedule for the patient. It is important to attend all scheduled infusions and to let the healthcare provider know if the patient misses an appointment or if have any problems with the infusion. The infusion should be given by a healthcare professional in a medical setting, such as a hospital or clinic. The infusion may take several hours, and the patient may experience some mild side effects, such as fever, redness or swelling at the infusion site, headache, or nausea. If the patient experiences severe side effects or an allergic reaction, they should be notified to the healthcare provider immediately. It is important to also keep a record of the treatment schedule, dosage, and any side effects that the patient may have.
Things to Do After Starting Laronidase for Mucopolysaccharidosis Type I (MPS I):
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Keep all appointments with the healthcare provider ready: It is essential to attend all scheduled appointments to monitor the condition and adjust the treatment as needed.
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Keep a treatment journal: Keep track of the treatment schedule, dosage, and side effects. This will help the healthcare provider make necessary adjustments to the treatment plan.
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Let the healthcare provider know if any appointment has been missed: if an appointment has been missed, let the healthcare provider know as soon as possible to schedule a new one.
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Report any side effects such as redness or swelling at the infusion site, fever, headache, or nausea to the healthcare provider. If the patient experiences severe side effects or an allergic reaction, immediately seek medical attention.
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Following a healthy lifestyle by eating a healthy diet, and avoiding alcohol and smoking can help improve overall health and well-being.
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Keep an eye on the progression of the disease such as breathing difficulties, joint pain, or changes in overall health.
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Consider joining a support group for MPS type I as it can provide emotional support and help connect with others who are going through similar experiences.
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Be aware of the long-term effects of the disease and treatment as it is a progressive disease whose symptoms can get worse over time, even with treatment. It is important to be aware of the long-term effects of the disease and treatment and to work closely with the healthcare provider to manage them.
Look Out for the Side Effects:
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Laronidase is a medication used to treat MPS I, which is caused by a deficiency of the enzyme alpha-L-iduronidase. Laronidase is a recombinant form of the enzyme that breaks down the buildup of glycosaminoglycans in the body.
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Common side effects of Laronidase include vomiting, nausea, joint pain (arthralgia), diarrhea, fast heart rate (tachycardia), abdominal pain, high blood pressure, redness of the skin (erythema), and bluish color of the skin or mucous membranes (cyanosis). These side effects are generally mild to moderate in intensity and usually go away within a few days.
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It is important to note that Laronidase is not a cure for MPS I, but it can help to improve some symptoms and slow the progression of the disease.
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There are no known drug interactions with Laronidase. However, it is essential to consult with a doctor before taking any new medications or supplements while taking Laronidase.
For Doctors
Indication:
Laronidase is used to treat MPS I, that lacks the enzyme alpha-L-iduronidase. The medication is a form of enzyme replacement therapy, which replaces the missing enzyme in the body. It is indicated for long-term treatment of the non-neurological manifestations of MPS I, which can include joint stiffness, an enlarged liver and spleen, a distinctive facial appearance, and heart problems. It is administered via intravenous infusion, typically once a week. It is important to note that this drug is not a cure for MPS I, but it can help to improve some symptoms and slow the progression of the disease. It is also important to check with a doctor before starting the treatment to ensure that the person is a confirmed diagnosis of MPS I.
Pharmacology
Mechanism of Action:
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MPS I is caused by a deficiency of alpha-L-iduronidase (IDUA), an enzyme that is responsible for breaking down and removing certain complex sugars called glycosaminoglycans (GAGs). When IDUA is deficient, GAGs build up in the body, causing a wide range of symptoms that can affect many different organs and systems.
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IDUA is an enzyme that is responsible for breaking down and removing certain complex sugars called glycosaminoglycans (GAGs) from the body. IDUA is a lysosomal enzyme that cleaves the alpha-L-iduronic acid from the non-reducing ends of the GAGs. The deficiency of IDUA can be treated by replacing the missing enzyme with a recombinant form of human IDUA called Laronidase.
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Laronidase works by replacing the missing IDUA enzyme, which helps break down and remove the accumulated GAGs (glucosaminoglycans). This reduces the symptoms of MPS I, such as enlarged organs, joint stiffness, and breathing difficulties.
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The treatment should be started as soon as the diagnosis is confirmed to prevent or slow down the progression of the disease. Laronidase is typically administered by intravenous (IV) infusion, which means it is given directly into the bloodstream through a vein.
Pharmacodynamics:
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The pharmacodynamic effects of Laronidase have been assessed by analyzing alterations in urinary GAG levels in patients with Mucopolysaccharidosis type I (MPS I). GAGs (glycosaminoglycans) are complex sugars that accumulate in the body in MPS I due to a deficiency of the enzyme IDUA (alpha-L-iduronidase).
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Laronidase works by replacing the missing IDUA enzyme, which helps break down and remove the accumulated GAGs. Studies have shown that treatment with Laronidase can significantly reduce urinary GAG levels, indicating that the drug is effectively breaking down and removing the accumulated GAGs. This reduction in GAG levels has been linked to improvements in symptoms such as breathing difficulties, joint stiffness, and enlarged organs.
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It is important to note that the reduction of urinary GAG levels does not necessarily mean that the disease is cured but that the drug is working and the GAGs are being removed from the body. Regular monitoring of the levels and symptoms is important to adjust the treatment as needed.
Absorption:
Laronidase is a medication that is given by intravenous (IV) infusion, which means it is administered directly into the bloodstream through a vein. Because it is not taken orally, it does not undergo the usual process of absorption through the gastrointestinal tract. After the IV infusion, Laronidase is rapidly distributed to the various tissues and organs of the body, including the liver, spleen, and bones. The enzyme is then able to enter cells and reach the lysosomes, where it can begin breaking down and removing the accumulated glycosaminoglycans (GAGs) that cause the symptoms of Mucopolysaccharidosis type I (MPS I).
Metabolism:
The pharmacokinetics (PK) of Laronidase have been studied in clinical trials and it has been found that the enzyme has a low clearance and a long half-life, which means that it stays in the body for a long time after the infusion. This allows for once-a-week dosing, which is convenient for patients. It is important to note that the efficacy of Laronidase treatment is not dependent on its plasma concentration but on the levels of lysosomal alpha-L-iduronidase activity in the target cells, which is achieved through its cellular uptake and delivery to the lysosome where it can exert its enzymatic activity.
Elimination:
The pharmacokinetics (PK) of Laronidase have been evaluated in clinical trials in patients six years and over. The mean plasma clearance, which is a measure of how quickly the drug is removed from the bloodstream, ranged from 1.7 to 2.7 ml/min/kg. The mean half-life, for half of the drug to be removed from the body, ranges from 1.5 to 3.6 hours.
These findings suggest that Laronidase is rapidly distributed to the various tissues and organs of the body and that it has a low clearance and a long half-life. This allows for once-a-week dosing, which is convenient for patients, and also supports the idea that the efficacy of Laronidase treatment is not dependent on its plasma concentration, but on the levels of lysosomal alpha-L-iduronidase activity in the target cells.
Indications and Uses:
Enzyme replacement therapy (ERT) using Laronidase is a treatment option for mucopolysaccharidosis type I (MPS I), and it is performed by administering the enzyme once a week via intravenous (IV) infusion. The duration of the treatment may vary depending on the individual case and the severity of the disease.
In addition to the regular ERT, Laronidase is also used as a pre-treatment for hematopoietic stem cell transplantation (HSCT) in patients with MPS I. The HSCT is a treatment option for MPS I that aims to replace the patient's deficient cells with healthy cells from a donor.
Prior to the transplant, Laronidase therapy is performed for 12 weeks to reduce the levels of accumulated GAGs in the body and to decrease the risk of pulmonary complications. After the transplant, the therapy is continued for eight weeks to support the engraftment of the healthy cells and to reduce the risk of complications. It is important to note that HSCT is a complex and risky procedure, and it should only be performed in specialized centers with experience in treating MPS I and other rare diseases.
Warnings and Precautions:
Increase in the Risk of Side Effects- Before receiving Laronidase, it is important to inform the healthcare provider if there have been any pre-existing medical conditions, such as heart disease, kidney disease, lung disease, seizures, migraine headaches, or sleep apnea. These conditions may affect the body's response to the medication and may increase the risk of side effects.
Allergic Reactions- Laronidase can cause allergic reactions in some people, which can range from mild to severe. Be aware of the signs of a severe allergic reaction, such as chest discomfort, sweating, pale skin, and trouble breathing. If the patient experiences any of these symptoms during or shortly after the infusion, they should immediately tell the health care providers and seek emergency medical help. To help prevent allergic reactions, doctors may also prescribe other medications, such as antihistamines or steroids. It is important to take all of the medications as directed and to inform the healthcare provider if any new symptoms or side effects appear.
Dosage Strength and Forms: Laronidase is available in the form of a powder for reconstitution and a solution for injection. The powder is reconstituted with sterile water before administration. The solution for injection is administered as an intravenous (IV) infusion.
The recommended dosage for Laronidase is 0.58 mg/kg of body weight, administered once a week. The dosage may be adjusted based on the individual case and the severity of the disorder. The treatment should be started as soon as the diagnosis is confirmed to prevent or slow down the progression of the disease. However, the dosage and duration of the treatment may vary depending on the individual case and the disorder's severity. It is important to work closely with a healthcare provider to monitor progress and adjust the treatment as needed.
Dosage and Administration:
The dosage is the same in adults and children six months or older. The dosage for Laronidase is 0.58 mg/kg intravenously once a week.
Contraindications:
Allergic Reaction: Laronidase should not be used in patients who have had a severe allergic reaction to the drug or its components.
Active Infection: Laronidase should not be used in patients with an active infection, as the drug may increase the risk of infection.
Pregnancy and Breastfeeding: Laronidase should not be used in pregnant or breastfeeding women, as the safety of the drug in these populations has not been established.
Hematopoietic Stem Cell Transplantation: Laronidase should not be used in patients who are scheduled for or have recently undergone hematopoietic stem cell transplantation, as the drug may increase the risk of complications.
Other Medical Conditions: Laronidase should not be used in patients with certain medical conditions, such as severe anemia, thrombocytopenia, or disseminated intravascular coagulation, as these conditions may increase the risk of bleeding or other complications.
Drug Interactions:
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Laronidase is a medication that is given by intravenous (IV) infusion, and it is not known to interact with other medications when given alone. However, it is essential to inform the healthcare provider about all the medications, vitamins, supplements, and herbal products that the patient is taking, as some of them may interact with the drug or the underlying condition.
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Laronidase is a protein, and it may interact with other proteins or molecules that are present in the blood. For example, it is not recommended to be given blood products such as albumin, since it may lead to a decrease in the activity of Laronidase.
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Patients who are receiving Laronidase should be closely monitored for any changes in the efficacy of their other treatments and any potential side effects. The healthcare provider should be informed of any new medications, supplements, or herbal products.
Laronidase During Pregnancy:
The safety and efficacy of Laronidase in pregnant women have not been established. However, as MPS I symptoms can get worse during pregnancy, it may be beneficial to continue treatment with Laronidase during pregnancy to prevent or slow down the progression of the disease. The benefits of treating MPS I during pregnancy should be weighed against any potential risks to the mother and the baby. The safety and efficacy of Laronidase for use during pregnancy should be discussed with a healthcare provider and a specialist in MPS I, as well as an obstetrician.
Breastfeeding and Laronidase:
The safety and efficacy of Laronidase in breastfeeding women have not been established. However, as MPS I symptoms can get worse during breastfeeding, it may be beneficial to continue treatment with Laronidase during breastfeeding to prevent or slow down the progression of the disease.
Laronidase in Geriatric Patients:
The safety and efficacy of Laronidase in geriatric patients have not been specifically studied. However, the pharmacokinetics of Laronidase has been studied in adult patients and no age-related differences in the safety or efficacy of the drug have been observed. Geriatric patients may be more susceptible to certain side effects of the drug, such as infections, so it is important for them to be closely monitored for any potential side effects.
