Abstract:
BACKGROUND:Mucopolysaccharidosis type I (MPS I) is a debilitating hereditary disease characterized by alpha-L-iduronidase (IDUA) deficiency and consequent inability to degrade glycosaminoglycans. The pathological accumulation of glycosaminoglycans systemically results in severe mental retardation and multiple organ dysfunction. Enzyme replacement therapy with recombinant human alpha-L-iduronidase (rhIDU) improves the function of some organs but not neurological deficits owing to its exclusion from the brain by the blood-brain barrier (BBB). METHODS:We divided MPS I mice into control group, enzyme replacement group with rhIDU 2.9 mg/kg injection, enzyme replacement with one-spot ultrasound treatment group, and enzyme replacement with two-spot ultrasound treatment group, and compare treatment effectiveness between groups. All ultrasound treatments were applied on left side brain. Evans blue was used to simulate the distribution of rhIDU in the brain. RESULTS:Transcranial pulsed weakly focused ultrasound combined with microbubbles facilitates brain rhIDU delivery in MPS I mice receiving systemic enzyme replacement therapy. With intravenously injected rhIDU 2.9 mg/kg, the IDUA enzyme activity on the ultrasound treated side of the cerebral hemisphere raised to 7.81-fold that on the untreated side and to 75.84% of its normal value. Evans blue simulation showed the distribution of the delivered drug was extensive, involving a large volume of the treated cerebral hemisphere. Two-spot ultrasound treatment scheme is more efficient for brain rhIDU delivery than one-spot ultrasound treatment scheme. CONCLUSIONS:Transcranial pulsed weakly focused ultrasound can open BBB extensively and facilitates brain rhIDU delivery. This novel technology may provide a new MPS I treatment strategy.
journal_name
Orphanet J Rare Disjournal_title
Orphanet journal of rare diseasesauthors
Hsu YH,Liu RS,Lin WL,Yuh YS,Lin SP,Wong TTdoi
10.1186/s13023-017-0649-6subject
Has Abstractpub_date
2017-06-08 00:00:00pages
109issue
1issn
1750-1172pii
10.1186/s13023-017-0649-6journal_volume
12pub_type
杂志文章abstract:PURPOSE:Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
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abstract::We report a male child with Oromandibular-limb hypogenesis (OMLH), the main features being bilateral sixth and seventh nerve palsies, limb anomalies and hypoplasia of the tongue. Additional features were shortness of the neck associated with torticollis. Radiographs of the cervical spine were non-contributory, but 3D ...
journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
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更新日期:2018-07-16 00:00:00
abstract::Paediatric chordomas are rare malignant tumours arising from primitive notochordal remnants with a high rate of recurrence. Only 5 % of them occur in the first two decades such less than 300 paediatric cases have been reported so far in the literature. In children, the average age at diagnosis is 10 years with a male-...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
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abstract:BACKGROUND:Rapamycin has gained significant attention for its potential activity in reducing the size of TSC-associated tumors, thus providing alternative to surgery. This study aimed at determining the efficacy of rapamycin and rapalogs for reducing the size of TSC-associated solid tumors in patients with Tuberous Scl...
journal_title:Orphanet journal of rare diseases
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abstract:BACKGROUND:Most patients with alpha-1 antitrypsin deficiency remain undiagnosed and therefore do not benefit from current therapies or become eligible for research studies of new treatments under development. Improving the detection rate for AATD is therefore a high priority for the Alpha-1 Foundation. A workshop was h...
journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
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abstract:BACKGROUND:Currently, clinical trials for new therapeutic strategies are being planned for Duchenne and Becker muscular dystrophies (DMD/BMD). However, it is difficult to obtain adequate numbers of patients in clinical trials. As solutions to these problems, patient registries are an important resource worldwide, espec...
journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,多中心研究
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
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journal_title:Orphanet journal of rare diseases
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
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abstract:BACKGROUND:Neurofibromatosis type 1 is an inherited condition with variable phenotypic expression and a high medical and social burden. The objectives of this patient survey were to better understand the real-world experiences of patients living with cutaneous neurofibromas (cNF), to perceive their satisfaction and fee...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
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更新日期:2019-12-04 00:00:00
abstract:BACKGROUND:Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric problems, microcephaly, motor defi...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-1329-5
更新日期:2020-02-27 00:00:00
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
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更新日期:2018-11-03 00:00:00
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journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-123
更新日期:2013-08-14 00:00:00
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pub_type: 杂志文章
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更新日期:2013-11-15 00:00:00