Mucopolysaccharidosis type I is a rare inherited condition that progressively affects many parts of the body, from bones and organs to the brain and heart. Understanding treatment options—both well-established and those being researched in clinical trials—can help families and caregivers navigate the journey ahead and make informed decisions about managing symptoms and improving quality of life.

How Treatment Helps People Living with MPS I

When a child receives a diagnosis of Mucopolysaccharidosis type I, families often feel overwhelmed by uncertainty. Treatment for MPS I focuses on slowing the progression of the disease, managing symptoms, and helping affected individuals maintain the best possible quality of life. The approach depends heavily on whether the person has severe or attenuated (milder) MPS I, as well as their age and overall health status.

The main goals of treatment include reducing the buildup of harmful substances called glycosaminoglycans (GAGs) in the body’s cells, protecting organs from damage, preserving mobility and independence, and supporting cognitive development in children with severe forms. Because MPS I affects multiple organ systems—including the heart, lungs, bones, joints, eyes, and sometimes the brain—care usually involves a team of specialists working together.

Today, medical societies recognize specific treatments as standard care for MPS I, particularly enzyme replacement therapy and hematopoietic stem cell transplantation. At the same time, researchers continue exploring new therapies through clinical trials, including innovative approaches like gene therapy that aim to address the underlying genetic cause of the condition more directly.

Standard Treatments Currently Used for MPS I

The foundation of MPS I treatment rests on two main approaches that have been used for years and are recommended by international medical guidelines. These treatments work by either replacing the missing enzyme that people with MPS I lack or by providing healthy cells that can produce the enzyme naturally.

Enzyme Replacement Therapy

Enzyme replacement therapy (ERT) involves regular infusions of a manufactured version of the enzyme that people with MPS I cannot produce—alpha-L-iduronidase. The specific medication used is called laronidase, marketed under the brand name Aldurazyme. This therapy was approved in the United States and Europe in 2003 and has become a cornerstone of MPS I management.

Laronidase works by supplementing the body with the enzyme needed to break down accumulated GAGs in cells throughout the body. When the enzyme enters the bloodstream through an intravenous infusion, it travels to various organs and tissues where it helps reduce the toxic buildup causing symptoms. The therapy is given once weekly, typically at a hospital or infusion center, and each session takes several hours.

Studies have shown that enzyme replacement therapy can improve several important aspects of health in people with MPS I. Patients receiving laronidase often experience better walking capacity and can cover greater distances without becoming tired. Lung function typically improves, making breathing easier. The therapy also helps reduce the size of enlarged organs like the liver and spleen, and may slow the progression of heart valve problems.

However, ERT has important limitations. The enzyme molecules cannot cross the barrier between the bloodstream and the brain, meaning this treatment does not protect against cognitive decline in children with severe MPS I who experience developmental regression. Additionally, because the therapy addresses symptoms rather than the underlying genetic cause, it must continue throughout the person’s lifetime. Stopping treatment would allow GAG accumulation to resume.

Side effects from enzyme replacement therapy are generally manageable. Some people experience infusion-related reactions during or shortly after treatment, which can include fever, chills, headache, rash, or changes in blood pressure. These reactions often lessen over time or can be controlled with medications given before the infusion. Rarely, patients develop antibodies against the replacement enzyme, which may reduce its effectiveness.

Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation, often abbreviated as HSCT, is considered the standard of care specifically for children with severe MPS I. This procedure was previously known as bone marrow transplantation. It involves replacing the patient’s blood-forming stem cells with healthy donor cells that can produce the missing enzyme naturally.

The transplanted cells come from a carefully matched donor—often a sibling, but sometimes an unrelated person whose tissue type closely matches the patient. Once the healthy stem cells take hold in the recipient’s bone marrow, they begin producing blood cells that carry the working alpha-L-iduronidase enzyme. These enzyme-producing cells travel throughout the body and even reach the brain, unlike infused enzyme therapy.

For children with severe MPS I, stem cell transplantation offers a significant advantage: it can prevent or slow cognitive decline. Studies have shown that children who receive HSCT early—typically before age two and ideally before significant brain damage has occurred—can maintain normal intelligence or experience much less intellectual disability than untreated children. The therapy also addresses many physical symptoms, improving survival significantly.

The procedure itself is complex and carries serious risks. Before transplantation, patients undergo conditioning treatment with chemotherapy or radiation to prepare the body to accept donor cells. The transplant process requires several weeks in the hospital, and recovery takes months. Possible complications include graft rejection (when the body refuses the donor cells), graft-versus-host disease (when donor cells attack the recipient’s tissues), infections due to weakened immunity, and organ damage from conditioning treatments.

Despite these risks, children treated with HSCT generally live much longer than those who receive no treatment. Without intervention, children with severe MPS I typically die within the first decade of life from heart or breathing complications. Transplantation has transformed this outlook, with many patients surviving into adulthood. However, the therapy does not completely reverse skeletal problems already present, and patients often continue to experience joint stiffness and bone abnormalities.

For people with attenuated MPS I, stem cell transplantation is not typically recommended because the risks outweigh the benefits in milder disease. These patients usually manage well with enzyme replacement therapy combined with supportive care for specific symptoms as they arise.

Supportive and Symptomatic Care

Beyond these main treatments, people with MPS I require ongoing management of various complications affecting different body systems. This supportive care is essential for maintaining quality of life and preventing disability.

Many patients need regular monitoring of heart valve function, and some require surgical valve replacement when disease progresses. Sleep apnea—where breathing stops repeatedly during sleep due to airway narrowing—is common and may need treatment with breathing support devices or surgical procedures to widen the airway. Ear infections occur frequently, often leading to hearing loss that requires hearing aids.

Joint problems and loss of mobility are nearly universal in MPS I. Physical therapy and regular range-of-motion exercises help preserve joint function for as long as possible. Some patients benefit from night splints to prevent contractures (permanent tightening of muscles and tendons). Many develop carpal tunnel syndrome, where compressed nerves in the wrist cause numbness and weakness in the hands. Surgery can relieve this pressure.

Eye problems, particularly clouding of the cornea, can significantly impair vision. In some cases, corneal transplantation may restore sight. Regular eye examinations help detect problems early. Similarly, routine hearing tests are crucial because progressive hearing loss affects most people with MPS I, and early intervention with hearing aids can preserve communication abilities and quality of life.

Children with severe MPS I may need educational support services tailored to their cognitive abilities. Families benefit from connecting with social workers and counselors who understand the challenges of managing a progressive genetic condition. Pain management, anti-inflammatory medications, and oxygen therapy are sometimes necessary as disease advances.

Promising Therapies Being Tested in Clinical Trials

While current standard treatments have significantly improved outcomes for people with MPS I, they cannot cure the condition or fully prevent all complications. This has driven researchers to develop next-generation therapies that might address the disease more comprehensively. Several innovative approaches are now being tested in clinical trials around the world.

Gene Therapy Approaches

Gene therapy represents one of the most exciting frontiers in MPS I treatment research. This approach aims to correct the underlying genetic problem by delivering a working copy of the IDUA gene directly into the patient’s cells. If successful, gene therapy could potentially provide a one-time treatment that enables the body to produce the missing enzyme continuously, without need for weekly infusions or the risks of transplantation.

One gene therapy candidate in clinical development is OTL-203, being developed by Orchard Therapeutics and Kyowa Kirin. This therapy uses a modified, harmless virus to carry the correct IDUA gene into the patient’s own blood stem cells outside the body. After the gene is inserted, these genetically corrected cells are returned to the patient through a procedure similar to stem cell transplantation. The conditioning treatment required is often less intense than traditional HSCT, potentially reducing side effects.

Early clinical trials of OTL-203 have shown promising results. The therapy appears safe, and treated patients have shown sustained enzyme production. The genetically modified cells successfully travel throughout the body, including to the brain, where they can potentially prevent cognitive decline—addressing one of the major limitations of standard enzyme replacement therapy.

Another gene therapy under investigation is RGX-111, developed by REGENXBIO in partnership with Nippon Shinyaku. This approach differs from OTL-203 by delivering the therapeutic gene directly into the nervous system through injection into the cerebrospinal fluid that surrounds the brain and spinal cord. The goal is to target the central nervous system more effectively, addressing cognitive symptoms and spinal cord compression that are difficult to treat with other methods.

RGX-111 has been tested in Phase I/II clinical trials evaluating both safety and preliminary effectiveness. Researchers measure enzyme levels in cerebrospinal fluid, monitor GAG accumulation, and assess whether treated children show preserved or improved cognitive function compared to historical data from untreated patients. The therapy is designed to complement rather than replace enzyme replacement therapy or transplantation.

Next-Generation Enzyme Replacement

Scientists are also working to improve upon standard enzyme replacement therapy by developing modified enzymes that can reach more tissues, including the brain. One investigational therapy called JR-171, developed by JCR Pharmaceuticals, is a specially engineered version of the alpha-L-iduronidase enzyme designed to cross the blood-brain barrier—something standard laronidase cannot do.

JR-171 uses a technology that attaches the enzyme to a molecule that naturally transports substances across the protective barrier surrounding the brain. In theory, this would allow the enzyme to reach brain cells and prevent or reduce cognitive decline, potentially offering benefits similar to stem cell transplantation but through a weekly infusion rather than a risky transplant procedure.

This therapy has moved through early clinical trials in Japan and other countries. Phase I studies focused on safety, measuring whether the modified enzyme caused any harmful reactions and confirming that it reached the central nervous system as intended. Subsequent Phase II trials have evaluated effectiveness by monitoring cognitive development in young children with severe MPS I who receive JR-171, comparing their progress to untreated historical patients.

If successful, brain-penetrating enzyme therapy could transform treatment for severe MPS I by providing the cognitive protection of transplantation without the associated risks. It might be used alone or in combination with standard enzyme replacement to address both physical and neurological symptoms comprehensively.

Cell-Based Gene Therapy

A different innovative approach being explored is ISP-001, developed by Immusoft Corporation. This therapy involves taking a patient’s own B cells—a type of white blood cell that normally produces antibodies—and genetically modifying them to produce the alpha-L-iduronidase enzyme. These engineered cells are then expanded in the laboratory and returned to the patient.

The advantage of this approach is that B cells naturally circulate throughout the body and have long lifespans. If they successfully produce enzyme continuously, patients might need only occasional cell infusions rather than weekly treatments. The mechanism relies on the body’s own cells acting as living factories for enzyme production, potentially offering more sustained and widespread enzyme delivery than standard ERT.

ISP-001 is still in earlier stages of development, with safety and proof-of-concept studies underway. Researchers are evaluating whether the modified B cells survive and produce enzyme at therapeutic levels, whether they can reduce GAG accumulation throughout the body, and what the safety profile looks like with repeated cell infusions over time.

Understanding Clinical Trial Phases

The experimental therapies described above progress through carefully structured testing phases before they can become standard treatments. Understanding these phases helps families know what to expect when considering clinical trial participation.

Phase I trials are the first tests in humans, primarily focused on safety. Researchers carefully monitor small groups of patients—often just a handful—to identify any harmful side effects, determine appropriate dosing, and understand how the body processes the therapy. These studies provide the first evidence of whether an experimental treatment reaches its target and shows any signs of working.

Phase II trials expand to larger groups of patients and focus more on effectiveness. Researchers measure specific outcomes—such as enzyme levels in blood or cerebrospinal fluid, GAG reduction in urine, changes in organ size, improvements in walking distance, or preservation of cognitive function. These studies help determine whether the therapy provides meaningful benefits and continues to be safe in more patients.

Phase III trials are large studies that compare the new therapy directly to current standard treatments or placebo. These trials generate the definitive evidence needed for regulatory approval. Hundreds of patients may participate across multiple countries. Researchers track both benefits and side effects carefully, and results from these studies determine whether a therapy becomes available to all patients.

For rare diseases like MPS I, where patient numbers are small, regulatory agencies sometimes allow accelerated approval pathways if early trial data show substantial promise. This means effective therapies may reach patients faster than the traditional timeline, though ongoing monitoring continues after approval.

Most Common Treatment Methods

• Enzyme Replacement Therapy (ERT)
  • Weekly intravenous infusions of laronidase (Aldurazyme) to replace the missing alpha-L-iduronidase enzyme
  • Helps break down accumulated glycosaminoglycans in cells throughout the body
  • Improves walking capacity, lung function, and reduces organ enlargement
  • Does not cross the blood-brain barrier and cannot prevent cognitive decline
  • Requires lifelong treatment with each infusion taking several hours
• Hematopoietic Stem Cell Transplantation (HSCT)
  • Replacing patient’s blood-forming stem cells with healthy donor cells that produce the missing enzyme
  • Considered standard of care for children with severe MPS I
  • Can prevent or slow cognitive decline when performed early, ideally before age two
  • Requires intensive conditioning treatment with chemotherapy or radiation
  • Carries significant risks including graft rejection, graft-versus-host disease, and infections
  • Significantly improves survival compared to no treatment
• Gene Therapy
  • OTL-203: Uses modified virus to insert working IDUA gene into patient’s own stem cells
  • RGX-111: Delivers therapeutic gene directly into cerebrospinal fluid to target central nervous system
  • Aims to provide one-time or infrequent treatment with continuous enzyme production
  • Potentially offers benefits similar to transplantation with lower risks
  • Currently in clinical trial phases, not yet approved as standard treatment
• Advanced Enzyme Replacement
  • JR-171: Modified enzyme designed to cross the blood-brain barrier
  • Could potentially prevent cognitive decline through weekly infusions
  • May combine advantages of ERT convenience with transplantation’s neurological protection
  • Under investigation in clinical trials in Japan and other countries
• Supportive Care
  • Physical therapy and range-of-motion exercises to preserve joint function
  • Surgical interventions for heart valve disease, airway obstruction, or carpal tunnel syndrome
  • Continuous positive airway pressure (CPAP) or surgery for sleep apnea
  • Hearing aids for progressive hearing loss
  • Corneal transplantation for vision impairment
  • Pain management and anti-inflammatory medications
  • Educational support services for children with cognitive involvement