| Title |
Development of idursulfase therapy for mucopolysaccharidosis type II (Hunter syndrome): the past, the present and the future
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2017
|
| DOI | 10.2147/dddt.s139601 |
| Pubmed ID | |
| Authors |
David AH Whiteman, Alan Kimura |
| Abstract |
Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare, multisystemic, progressive lysosomal storage disease caused by deficient activity of the iduronate-2-sulfatase (I2S) enzyme. Accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate results in a broad range of disease manifestations that are highly variable in presentation and severity; notably, approximately two-thirds of individuals are affected by progressive central nervous system involvement. Historically, management of this disease was palliative; however, during the 1990s, I2S was purified to homogeneity for the first time, leading to cloning of the corresponding gene and offering a means of addressing the underlying cause of MPS II using enzyme replacement therapy (ERT). Recombinant I2S (idursulfase) was produced for ERT using a human cell line and was shown to be indistinguishable from endogenous I2S. Preclinical studies utilizing the intravenous route of administration provided valuable insights that informed the design of the subsequent clinical studies. The pivotal Phase II/III clinical trial of intravenous idursulfase (Elaprase(®); Shire, Lexington, MA, USA) demonstrated improvements in a range of clinical parameters; based on these findings, intravenous idursulfase was approved for use in patients with MPS II in the USA in 2006 and in Europe and Japan in 2007. Evidence gained from post-approval programs has helped to improve our knowledge and understanding of management of patients with the disease; as a result, idursulfase is now available to young pediatric patients, and in some countries patients have the option to receive their infusions at home. Although ERT with idursulfase has been shown to improve somatic signs and symptoms of MPS II, the drug does not cross the blood-brain barrier and so treatment of neurological aspects of the disease remains challenging. A number of novel approaches are being investigated, and these may help to improve the care of patients with MPS II in the future. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 95 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 95 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 17 | 18% |
| Student > Bachelor | 13 | 14% |
| Student > Postgraduate | 9 | 9% |
| Other | 8 | 8% |
| Student > Master | 7 | 7% |
| Other | 16 | 17% |
| Unknown | 25 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 27 | 28% |
| Medicine and Dentistry | 15 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
| Agricultural and Biological Sciences | 4 | 4% |
| Neuroscience | 3 | 3% |
| Other | 9 | 9% |
| Unknown | 33 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 November 2023.
All research outputs
#7,124,952
of 25,604,262 outputs
Outputs from Drug Design, Development and Therapy
#458
of 2,271 outputs
Outputs of similar age
#103,703
of 328,070 outputs
Outputs of similar age from Drug Design, Development and Therapy
#6
of 47 outputs
Altmetric has tracked 25,604,262 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 2,271 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 328,070 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 47 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.