Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome)

Silva, Edina Mariko Koga da; Strufaldi, Maria Wany Louzada; Andriolo, Régis B; Silva, Laercio Antonio da

doi:10.1002/14651858.cd008185.pub4

Cited by 43 publications

(34 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Successful clinical development would provide immunomodulatory gene therapy in Pompe disease, which would induce immune tolerance to GAA and prevent HSAT formation. This strategy could be useful in other lysosomal storage disorders and in hemophilia, where antibody responses to therapeutic proteins frequently complicate replacement therapy 2, 35, 36, 37, 38, 39…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction

Han

Ronzitti

Arnson

et al. 2017

Molecular Therapy - Methods & Clinical Development

View full text Add to dashboard Cite

Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 1011 vector genomes [vg]/kg). Both treatments significantly reduced glycogen content of the heart and diaphragm. Although ERT triggered anti-GAA antibody formation, there was no detectable antibody response following AAV vector administration. The efficacy of three lower dosages of AAV2/8-LSPhGAA was evaluated in GAA-KO mice, either alone or in combination with ERT. The minimum effective dose (MED) identified was 8 × 1010 vg/kg to reduce glycogen content in the heart and diaphragm of GAA-KO mice. A 3-fold higher dose was required to suppress antibody responses to ERT. Efficacy from liver gene therapy was slightly greater in male mice than in female mice. Vector dose correlated inversely with anti-GAA antibody formation, whereas higher vector doses suppressed previously formed anti-GAA antibodies as late as 25 weeks after the start of ERT and achieved biochemical correction of glycogen accumulation. In conclusion, we identified the MED for effective AAV2/8-LSPhGAA-mediated tolerogenic gene therapy in Pompe disease mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction

Han

Ronzitti

Arnson

et al. 2017

Molecular Therapy - Methods & Clinical Development

View full text Add to dashboard Cite

show abstract

“…The severe phenotype, which is characterized by CNS involvement, is more than twice as prevalent as the attenuated form of the disease [3]. Progressive cardiac and airway disease, along with cognitive degeneration in severe cases, usually result in death during the first or second decade of life; whereas patients with the attenuated phenotype may survive into adulthood [1], [4].…”

Section: Introductionmentioning

confidence: 99%

Growth charts for patients with Hunter syndrome

Patel

Suzuki

Maeda

et al. 2014

Molecular Genetics and Metabolism Reports

View full text Add to dashboard Cite

Children with mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, an X-linked disorder, suffer from a multisystem dysfunction caused by the accumulation of glycosaminoglycans. However, there has been no systemic report on the growth of patients with MPS II. The purpose of this study is to describe the growth patterns of patients with MPS II and to compare with the patterns of age-matched controls. Data (height, weight, age, etc.) was collected in a longitudinal study of Japanese male patients with MPS II (n = 111). The mean birth length was 50.31 ± 1.42 cm, while the mean birth weight was 3.35 ± 0.39 kg. The mean final height and weight at 18 years and older were 125.63 ± 9.09 cm and 37.18 ± 8.72 kg; corresponding to a difference of − 46.40 cm and − 25.89 kg lower, when compared with healthy Japanese male controls. The mean birth BMI was 10.84 ± 3.29 kg/m2, while the mean BMI at 18 years was 29.41 ± 6.15 kg/m2. The growth pattern in patients with MPS II was characterized by overgrowth for the first several years, although growth velocity fell below that of the normal healthy controls after one year of age. No statistical difference in height was observed between patients with the attenuated and severe phenotypes in each age class.In conclusion, this report describes the natural history of growth in patients with MPS II, which can help in monitoring the progression of the disease as well as assessing therapeutic efficacy.

show abstract

“…These somatic improvements result in a better quality of life for some patients [29, 113]. However, conventional ERT does not alter the course of neurological decline [37,33, 112,114]. …”

Section: Treatmentmentioning

confidence: 99%

Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)

Stapleton

Kubaski

Mason

et al. 2017

Expert Opinion on Orphan Drugs

View full text Add to dashboard Cite

Introduction Mucopolysaccharidosis Type II (MPS II; Hunter syndrome) is an X- linked lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS). IDS deficiency leads to primary accumulation of dermatan sulfate (DS) and heparan sulfate (HS). MPS II is both multi-systemic and progressive. Phenotypes are classified as either attenuated or severe (based on absence or presence of central nervous system impairment, respectively). Areas covered Current treatments available are intravenous enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), anti-inflammatory treatment, and palliative care with symptomatic surgeries. Clinical trials are being conducted for intrathecal ERT and gene therapy is under pre-clinical investigation. Treatment approaches differ based on age, clinical severity, prognosis, availability and feasibility of therapy, and health insurance. This review provides a historical account of MPS II treatment as well as treatment development with insights into benefits and/or limitations of each specific treatment. Expert opinion Conventional ERT and HSCT coupled with surgical intervention and palliative therapy are currently the treatment options available to MPS II patients. Intrathecal ERT and gene therapy are currently under investigation as future therapies. These investigative treatments are critical to address the limitations in treatment of the central nervous system (CNS).

show abstract

Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome)

Abstract: Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome).

Cited by 43 publications

References 23 publications

Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction

Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction

Growth charts for patients with Hunter syndrome

Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)

Contact Info

Product

Resources

About