An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
鞘内酶替代治疗粘多糖贮积症 I 型认知衰退的推广研究
基本信息
- 批准号:9557579
- 负责人:
- 金额:$ 4.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:3 year oldAddressAdverse effectsAdverse eventAffectAgeAreaBiochemicalBlood - brain barrier anatomyBrainCanis familiarisCentral Nervous System AgentsCentral Nervous System DiseasesCerebrospinal FluidChildClinicalCognitionCognitiveCoupledDataDementiaDevelopmentDiffusionDiffusion Magnetic Resonance ImagingDiseaseEnzymesFiberFundingGlycosaminoglycansGoalsHeadacheHearingHematopoietic Stem Cell TransplantationHumanHydrocephalusImmune responseImpaired cognitionInheritedInstructionIntelligence TestsIntravenousL-IduronidaseLanguage DevelopmentLearningLongevityLongitudinal StudiesLysosomal Storage DiseasesMagnetic Resonance ImagingMarketingMeasuresMemoryMemory LossMental RetardationMorphologyMucopolysaccharidosis INamesNeuraxisNeurologic ExaminationNeurologic SymptomsNeuropsychological TestsNeuropsychologyOutcomeOutcome MeasureParticipantPathologicPatientsPhasePilot ProjectsProteinsRadiology SpecialtyRandomizedRecombinantsReportingSafetySchoolsSeveritiesStructureStudy SubjectSymptomsTeenagersTestingTimeTransplantationVisionVisitWalkingclinical carecognitive developmentdrug developmentemerging adultfallsfollow-upinnovationnervous system disorderneurobehavioralopen labelpre-clinical researchpreventprospectivescreeningspinal cord compressionsymptom treatmenttreatment effectwhite matter
项目摘要
"Mucopolysaccharidosis I (MPS I) is an inherited lysosomal storage disease due to deficiency of alpha-Liduronidase.
Recombinant human alpha-L-iduronidase (rhIDU) is available as laronidase (trade name
"Aldurazyme") for intravenous delivery to treat physical disease due to MPS I. While partially effective for
physical disease, intravenous rhIDU does not treat neurological symptoms of MPS I, because the blood-brain
barrier prevents the bulk of the administered protein from entering the central nervous system (CNS).
Patients with MPS I suffer from progressive neurological disease, including cognitive decline and dementia,
as well as spinal cord compression, hearing and vision problems, hydrocephalus and headaches. Our
preclinical research has found that intrathecal (IT) administration of rhIDU can disperse throughout the
neuraxis, reach deep brain structures and remove brain lysosomal storage in MPS I dogs. We have treated
a small number of MPS I subjects with IT rhIDU for disease-related spinal cord compression and have found
no significant safety concerns for this approach. Currently, we are conducting a 2-year randomized study of
IT rhIDU for cognitive decline in MPS I patients, which was funded as a pilot project by the LDN
(NCT008523580). This new project would permit a five-year extension study for participants in the pilot
project, which would allow us to collect long-term data on safety and efficacy. The primary safety outcome
measure will be the rate and severity of treatment-related adverse effects. The primary efficacy outcome
measure will be the mean intra-subject change in memory score between baseline and the subject's final
visit. Other important efficacy measures are changes in scores of tests of other neuropsychological domains
and changes in 3 Tesla brain magnetic resonance imaging (MRI) parameters, such as volumes, morphology,
diffusion abnormalities and white matter fiber tracking. Currently, there are no treatment options for the brain
in MPS I patients, except for the youngest, most severely affected patients, who may be considered for
hematopoietic stem cell transplantation. If successful, intrathecal rhIDU would bring major innovation to the
clinical care of MPS I patients.
粘多糖病I (MPS I)是一种遗传性溶酶体贮积病,由于缺乏- liduonidase。
项目成果
期刊论文数量(0)
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Agnes Huang Chen其他文献
Agnes Huang Chen的其他文献
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{{ truncateString('Agnes Huang Chen', 18)}}的其他基金
An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
鞘内酶替代治疗粘多糖贮积症 I 型认知衰退的推广研究
- 批准号:
8907060 - 财政年份:
- 资助金额:
$ 4.5万 - 项目类别:
An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
鞘内酶替代治疗粘多糖贮积症 I 型认知衰退的推广研究
- 批准号:
8934174 - 财政年份:
- 资助金额:
$ 4.5万 - 项目类别:
An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
鞘内酶替代治疗粘多糖贮积症 I 型认知衰退的推广研究
- 批准号:
9338314 - 财政年份:
- 资助金额:
$ 4.5万 - 项目类别:
An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
鞘内酶替代治疗粘多糖贮积症 I 型认知衰退的推广研究
- 批准号:
9146688 - 财政年份:
- 资助金额:
$ 4.5万 - 项目类别:
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