Advances In Treatments Available For Mucopolysaccharidoses (MPS)

Dr. Lagler begins by reviewing the landscape of lysosomal storage diseases, emphasizing the rarity of MPS conditions and the importance of early diagnosis. He outlines the seven recognized MPS types and their clinical variability, stressing that over 70% of patients have central nervous system (CNS) involvement—an important consideration when evaluating treatment efficacy.

He then delves into ERT, the current standard of care for several MPS subtypes. ERT is shown to be safe, well-tolerated, and effective at reducing glycosaminoglycan (GAG) levels, improving liver size, mobility, and lung function. However, its limitations are significant: ERT does not adequately address CNS symptoms, eye involvement, or bone pathology due to anatomical and physiological barriers, such as the blood-brain barrier and limited vascularization of skeletal tissue. Infusion reactions, although typically mild, are another consideration.

A major theme throughout the presentation is the critical importance of early intervention. Dr. Lagler shares evidence that earlier treatment initiation—especially in siblings identified pre-symptomatically—results in substantially better outcomes. Delays in diagnosis, especially in milder phenotypes, diminish ERT’s effectiveness and may lead to irreversible damage.

The session then explores emerging treatment modalities aimed at overcoming current ERT limitations. These include:

• Intrathecal ERT: Direct delivery into the CNS via lumbar puncture, with promising trial results for MPS I, II, and III.
• Pharmacological chaperones: Small molecules that stabilize misfolded enzymes and may cross the blood-brain barrier.
• Trojan horse strategies: Fusing therapeutic enzymes with transport molecules (e.g., insulin or transferrin receptors) to bypass the blood-brain barrier.
• Gene therapy: Both in vivo and ex vivo approaches are under clinical investigation for several MPS types. These aim for continuous enzyme production and potentially long-term correction.
• Encapsulated cell bioreactors: Implantable systems that secrete therapeutic enzymes.

Dr. Lagler concludes by underscoring the need for multidisciplinary care, with pediatricians playing a central role in coordinating long-term treatment and identifying disease progression. As therapies evolve, early recognition and coordinated care remain the cornerstones of optimal patient outcomes.

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