Mucopolysaccharidosis type I (MPS-I) is a rare, inherited metabolic disorder caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). This enzyme deficiency leads to the accumulation of glycosaminoglycans (GAGs) in various tissues and organs, resulting in progressive multi-systemic manifestations.
MPS-I encompasses three subtypes: Hurler syndrome (MPS-IH), Hurler-Scheie syndrome, and Scheie syndrome.
Current Treatment Landscape
The standard treatments for MPS-IH include:
- Enzyme Replacement Therapy (ERT): Recombinant human IDUA enzyme is administered intravenously to replace the deficient enzyme. While ERT can reduce somatic symptoms, it has limited efficacy in treating neurological manifestations due to the inability of the enzyme to cross the blood-brain barrier.
Aldurazyme (laronidase): The First-Line Approved Treatment for MPS-I - Sanofi
Aldurazyme is a recombinant human α-L-iduronidase enzyme developed by BioMarin Pharmaceutical Inc. and Sanofi. It was approved by the U.S. FDA in 2003 for use in patients with Mucopolysaccharidosis Type I, including Hurler (MPS-IH), Hurler-Scheie, and Scheie syndromes.
Administration & Dosage
- Form: Intravenous (IV) infusion.
- Dosage: 2.9 mg/5 mL (0.58 mg/mL) of laronidase in a single-dose vial.
- Lifelong Therapy: Administered for the patient’s lifetime unless contraindicated or replaced by more definitive therapy like stem cell transplant or gene therapy.
- Hematopoietic Stem Cell Transplantation (HSCT): This procedure involves infusing hematopoietic stem cells from a healthy donor to provide a source of functional IDUA enzyme. HSCT can address both somatic and some neurological symptoms, but carries risks such as graft-versus-host disease and limited availability of suitable donors.
Despite these options, there remains a significant unmet need for therapies that can effectively address the neurological aspects of MPS-IH.
Emerging Therapies and Innovations
1. OTL-203 (Orchard Therapeutics/Kyowa Kirin)
- OTL-203 is an investigational ex vivo autologous gene therapy.
- It uses a modified virus to insert a functional copy of the IDUA gene into a patient’s cells.
- Received orphan, rare pediatric disease designation & Fast Track designation from the US FDA and Priority Medicines (PRIME) status from the European Medicines Agency.
- The HURCULES study, a registrational trial evaluating the efficacy and safety of OTL-203, is currently enrolling patients in the U.S. and Europe.
2. lepunafusp alfa (JR-171) - JCR Pharmaceuticals
- It is a fusion protein consisting of humanized anti-human transferrin receptor (hTfR) antibody Fab and IDUA, which is designed to facilitate cellular uptake and BBB penetration by binding to hTfR.
- It is administered as an IV infusion and is in the Phase I/II clinical stage of development.
3. ISP-001 (Autologous Plasmablasts (B cells) - Immusoft of CA
- It comprises autologous plasmablasts (B cells) engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty (SB) transposon system.
- Currently, it is in the Phase I clinical stage of development.
- Received orphan and rare pediatric disease designation from the US FDA.
Competitive Landscape and Market Implications
The development of new therapies for MPS-IH is highly competitive, with multiple companies advancing innovative treatments. The success of these therapies will depend on factors such as:
- Efficacy: The ability to effectively treat both somatic and neurological symptoms.
- Safety: Minimizing risks and side effects associated with treatment.
- Accessibility: Ensuring that therapies are available and affordable for patients worldwide.
As clinical trials progress and regulatory approvals are pursued, the landscape of MPS-IH treatment is poised for significant transformation, offering hope for improved outcomes and quality of life for affected individuals.
Looking Ahead
The future of MPS-IH treatment is promising, with advancements in gene therapy, Cell therapy, and targeted enzyme replacement strategies offering the potential for more effective and durable solutions. Continued research, collaboration, and investment in these innovative therapies are essential to address the unmet needs of patients and families affected by this devastating condition.
