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Updated: Jun 8, 2026
Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice
Published on: October 3, 2011
Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
Vinicia Assunta Polito1, Serena Abbondante, Roman S Polishchuk
1Telethon Institute of Genetics and Medicine (TIGEM), CNR, via P. Castellino 111, Naples 80131, Italy.
Abstract:
Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, is a devastating disorder associated with a shortened life expectancy. Patients affected by MPSII have a variety of symptoms that affect all organs of the body and may include progressive cognitive impairment. MPSII is due to inactivity of the enzyme iduronate-2-sulfatase (IDS), which results in the accumulation of storage material in the lysosomes, such as dermatan and heparan sulfates, with consequent cell degeneration in all tissues including, in the severe phenotype, neurodegeneration in the central nervous system (CNS). To date, the only treatment available is systemic infusion of IDS, which ameliorates exclusively certain visceral defects. Therefore, it is important to simultaneously treat the visceral and CNS defects of the MPSII patients. Here, we have developed enzyme replacement therapy (ERT) protocols in a mouse model that allow the IDS to reach the brain, with the substantial correction of the CNS phenotype and of the neurobehavioral features. Treatments were beneficial even in adult and old MPSII mice, using relatively low doses of infused IDS over long intervals. This study demonstrates that CNS defects of MPSII mice can be treated by systemic ERT, providing the potential for development of an effective treatment for MPSII patients.
Insights
Enzyme replacement therapy (ERT) successfully delivered iduronate-2-sulfatase (IDS) to the brain in MPSII mice, correcting neurobehavioral deficits. This approach offers a promising new treatment for Hunter syndrome
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, is a lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency.
- MPSII leads to progressive multi-organ damage, including neurodegeneration and cognitive impairment in severe cases.
- Current treatments for MPSII primarily address visceral symptoms, leaving central nervous system (CNS) defects largely untreated.
Purpose of the Study:
- To develop and evaluate enzyme replacement therapy (ERT) protocols for delivering IDS to the CNS in a mouse model of MPSII.
- To assess the efficacy of systemic IDS-ERT in correcting CNS and neurobehavioral phenotypes in MPSII mice.
Main Methods:
- Development of ERT protocols using systemic infusion of IDS in MPSII mouse models.
- Evaluation of IDS brain penetration and correction of CNS pathology and neurobehavioral deficits.
- Testing treatment efficacy in adult and aged MPSII mice.
Main Results:
- Systemic ERT enabled IDS to reach the brain in MPSII mice, substantially correcting CNS phenotypes.
- Significant improvements in neurobehavioral features were observed following IDS-ERT.
- Therapeutic benefits were demonstrated even in adult and old MPSII mice with relatively low IDS doses and long treatment intervals.
Conclusions:
- Systemic enzyme replacement therapy can effectively treat central nervous system defects in MPSII.
- This study provides a foundation for developing effective ERT strategies for MPSII patients, addressing both visceral and CNS manifestations.
- The potential for treating adult and aged MPSII patients with this approach is significant.
