Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label,...

Area of Science:

• Neurology
• Genetics
• Biochemistry

Background:

• Central nervous system (CNS) manifestations in mucopolysaccharidosis type I (MPS I), including cognitive impairment, are poorly addressed by standard intravenous enzyme replacement therapy (ERT) with laronidase.
• Hematopoietic stem cell transplantation can treat neurological symptoms but is not typically used for attenuated MPS I cases.

Purpose of the Study:

• To evaluate the efficacy of intrathecal laronidase in treating cognitive impairment in adults with attenuated MPS I.

Main Methods:

• A randomized, open-label, controlled pilot study involving eight attenuated MPS I patients with cognitive impairment (aged 12-50 years).
• All participants had prior intravenous laronidase treatment; weekly intravenous laronidase continued throughout the study.
• A one-year randomization period followed by an additional year of treatment for all participants, with cognitive assessments conducted over 24 months.

Main Results:

• No significant differences in neuropsychological assessment scores were observed between the intrathecal laronidase treatment group and the control group over the one-year randomized period or at 18 and 24 months.
• The control group also showed no significant decline in cognitive scores.
• Adverse events included pain, headache, neck spasm, and transient blurry vision; one serious adverse event (headache) was possibly related to the treatment.

Conclusions:

• Intrathecal laronidase did not demonstrate a significant effect on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period.
• Further investigation in a five-year open-label extension study is ongoing.