Treatments & Care Of Mucopolysaccharidoses (MPS) In Children

Prof. Giugliani begins by explaining how MPS results from enzyme deficiencies that disrupt the degradation of glycosaminoglycans (GAGs), leading to multisystemic GAG accumulation. The two main approved therapies are hematopoietic stem cell transplantation (HSCT), used primarily in severe MPS I, and intravenous enzyme replacement therapy (ERT), available for MPS I, II, IVa, VI, and VII. ERT improves somatic symptoms such as hepatosplenomegaly, respiratory function, endurance, and joint mobility but has limited impact on the CNS, heart valves, bones, and corneal clouding.

The session explores several alternative approaches to address these limitations:

• Small molecules like genistein and pentosan polysulfate have shown mixed or limited results.
• Intrathecal and intracerebroventricular ERT were trialed to bypass the blood-brain barrier, with limited success. However, intracerebroventricular ERT is now approved in Japan for MPS II.
• Fusion protein ERT using “Trojan horse” technology shows promise. These therapies are able to cross the blood-brain barrier and reduce CSF GAG levels. One such treatment is approved in Japan for MPS II, with others in development for MPS I and III.
• Encapsulated cell therapy delivers cells engineered to secrete enzymes, implanted surgically to provide continuous enzyme release without weekly infusions.

Prof. Giugliani then details gene therapy strategies, including:

• Ex vivo gene therapy, where patient cells are modified in the lab and reintroduced.
• In vivo approaches, using viral vectors (e.g., AAV9) to deliver therapeutic genes to the brain or liver. Notably, intracisternal injections (into the cisterna magna) offer promising CNS biodistribution.

He presents therapy development status across MPS subtypes and highlights that MPS I and II have the most advanced programs. He concludes by stressing that early diagnosis—ideally through newborn screening—remains the greatest determinant of treatment success, especially before CNS damage becomes irreversible.

Dr. Lampe adds that care must also include symptomatic management, surgery, physical therapy, and psychological support to maximize quality of life in this chronic, progressive group of disorders.

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