Emerging Therapies in Mucopolysaccharidosis Type I: 4 Breakthroughs on the Horizon

While current treatments such as enzyme replacement therapy (ERT) have helped manage symptoms, significant limitations remain, especially for neurological involvement. Fortunately, the Mucopolysaccharidosis Type I treatment pipeline is now filled with promising new approaches, with four therapies standing out for their innovation and potential impact.

1. Gene Therapy: Addressing the Root Cause

Among the most exciting developments is gene therapy, which offers the possibility of a one-time treatment that corrects the underlying genetic defect.

Sanofi’s MPS I program is pioneering the use of adeno-associated virus (AAV) vectors to deliver functional copies of the IDUA gene directly to the liver. This turns the liver into a long-term source of the missing enzyme. Early clinical data show promise in restoring enzyme levels and reducing GAG accumulation.

This gene therapy approach could represent a shift in the future of MPS I treatment, moving from chronic management to potential long-term correction.

2. Intrathecal ERT: Overcoming the Brain Barrier

A significant drawback of standard ERT is its inability to reach the brain, leaving cognitive symptoms largely untreated. Intrathecal enzyme replacement therapy (IT ERT) delivers the enzyme directly into the cerebrospinal fluid, bypassing the blood-brain barrier.

Several ISP therapies are using this method to address the neurological effects of MPS I. Ongoing mucopolysaccharidosis I clinical trials have demonstrated improvements in cognitive outcomes and central nervous system (CNS) biomarkers, showing potential for broader symptom control.

3. Stem Cell-Based Gene Therapy: Long-Term Effects

Another cutting-edge approach is hematopoietic stem cell gene therapy (HSC-GT), in which a patient’s own stem cells are modified to produce the missing enzyme. These cells are then reinfused, providing a long-lasting internal enzyme source.

Programs by companies like Orchard Therapeutics are currently under investigation. This therapy may also offer some CNS benefits, as enzyme-secreting cells migrate into the brain.

As part of the Mucopolysaccharidosis Type I treatment pipeline, HSC-GT holds great promise for newly diagnosed patients, especially if implemented early in life.

4. Substrate Reduction Therapy: Simplifying Treatment

Substrate reduction therapy (SRT) is gaining traction as a complementary or standalone approach. Instead of supplying the missing enzyme, SRT reduces the production of GAGs, minimizing their accumulation.

These orally administered drugs offer greater convenience and can be used alongside ERT or gene therapy. As one of the newer ISP therapies, SRT is currently being evaluated in several mucopolysaccharidosis I clinical trials.

Paving the Way Forward

As the field evolves, Sanofi’s MPS I program and other companies are advancing therapies that could dramatically alter the standard of care. The four treatment approaches—gene therapy, IT ERT, HSC-GT, and SRT—highlight the robust pipeline that aims to go beyond symptom management.

The future of MPS I treatment is no longer just about extending life, but about improving its quality—physically, neurologically, and emotionally.