Defining ichthyosis in Sjogren-Larsson syndrome for clinical trial preparedness
Defining ichthyosis in Sjogren-Larsson syndrome for clinical trial preparedness
批准号:
10292301
负责人:
WILLIAM B. RIZZO
金额:
$22.32万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-08-10 至 2023-07-31
关键词:
AddressAlcoholsAldehydesAllelesApplications GrantsBiochemicalBiological MarkersBirthBlindedBrain DiseasesCaringCholesterolClinicalClinical TrialsComplementCongenital ichthyosisConsumptionCutaneousDefectDiseaseEffectivenessElasticityEnzymesEthersEvaluationExclusionFDA approvedFatty AlcoholsFrequenciesFutureGenotypeGoalsInstitutionIntellectual functioning disabilityJudgmentKnowledgeLifeLipidsLittle&aposs DiseaseLotionMeasurementMeasuresMedical centerMembraneMetabolicMetabolismMethodsModalityMonitorMulticenter StudiesMutationNatural HistoryPathogenesisPathogenicityPatientsPharmaceutical PreparationsPharmacotherapyPhase II Clinical TrialsPhenotypePlacebosPopulationPrevalencePropertyRare DiseasesReadinessResearchRetinal DiseasesSeizuresSeveritiesSjogren-Larsson SyndromeSkinSkin TissueStratum corneumStructureSurrogate MarkersSymptomsSystemTestingTherapeuticTherapeutic TrialsThickTimeTissuesTopical applicationTreatment EfficacyUltrasonographyUncertaintyVariantVisualWateradductbasebiochemical toolsdisease-causing mutationdisorder of macula of retinaeffective therapyelastographyfatty aldehydegene therapyin vivoindexinginnovationinstrumentationlong-chain-aldehyde dehydrogenasenovelpartial responsepotential biomarkerpreventrecruitskin disorderspasticitysuccess
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Sjögren-Larsson syndrome (SLS) is a rare neurocutaneous disease caused by mutations in ALDH3A2 and associated with
deficient activity of fatty aldehyde dehydrogenase (FALDH). Symptoms of SLS include congenital ichthyosis, spastic
diplegia, intellectual disability, and a distinctive retinopathy. FALDH deficiency results in accumulation of fatty alcohols,
ether glycerolipids (alkylglycerols) and cholesterol in the stratum corneum. The prevalence of SLS is estimated to be
1:250,000.
There are no FDA-approved drugs for SLS or other forms of ichthyosis. Although clinical trials in SLS based on the known
enzymatic and biochemical defects are just now beginning, evaluation of treatment efficacy for the cutaneous
symptoms suffers from an imprecise measure of ichthyosis severity, which currently relies on subjective clinical
judgment alone, and lack of an effective cutaneous biomarker. We propose to address this weakness for future clinical
trials of SLS by applying innovative methods for objectively measuring ichthyosis severity and characterizing newly
discovered lipid abnormalities in the skin.
A population of 15 SLS subjects will be recruited from those already followed at our institution as part of a longitudinal
natural history study of SLS. We will define skin thickness and elasticity using innovative high frequency ultrasound
methods with shear wave elastography, characterize functional abnormalities in the epidermal water barrier, score
clinical severity of the ichthyosis using a validated clinical scoring system, and determine whether these measures
correlate with stratum corneum lipid content of alkylglycerols and cholesterol. When completed, these studies will
define the structural and functional severity of ichthyosis in Sjögren-Larsson syndrome and potentially identify lipid
biomarkers that will be important for clinical trials.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Sjogren-Larsson Syndrome: a Longitudinal Study of Natural History
-
批准号:9348661
-
项目类别:
-
资助金额:$12.0万
-
财政年份:2009
-
负责人:WILLIAM B. RIZZO
-
依托单位:
Sterol and Isoprenoid Diseases Consortium
-
批准号:8765237
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项目类别:
-
资助金额:$90.0万
-
财政年份:2009
-
负责人:WILLIAM B. RIZZO
-
依托单位:
Sjogren-Larsson Syndrome: a Longitudinal Study of Natural History
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批准号:8936524
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项目类别:
-
资助金额:$18.0万
-
财政年份:2009
-
负责人:WILLIAM B. RIZZO
-
依托单位:
Sterol and Isoprenoid Diseases Consortium
-
批准号:9348659
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项目类别:
-
资助金额:$60.0万
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财政年份:2009
-
负责人:WILLIAM B. RIZZO
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依托单位:
PHENOTYPIC VARIATION IN SJOGREN LARSSON
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批准号:6304936
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项目类别:
-
资助金额:$0.06万
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财政年份:1999
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负责人:WILLIAM B. RIZZO
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依托单位:
PHENOTYPIC VARIATION IN SJOGREN LARSSON
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批准号:6264249
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项目类别:
-
资助金额:$0.06万
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财政年份:1998
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负责人:WILLIAM B. RIZZO
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依托单位:
Ichthyosis in Sjogren-Larsson syndrome
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批准号:7425542
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项目类别:
-
资助金额:$0.29万
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财政年份:1997
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负责人:WILLIAM B. RIZZO
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依托单位:
MOLECULAR GENETICS OF SJOGREN LARRSON SYNDROME
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批准号:6245989
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项目类别:
-
资助金额:$2.76万
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财政年份:1997
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负责人:WILLIAM B. RIZZO
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依托单位:
ICHTHYOSIS IN SJOGREN/LARSSON SYNDROME
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批准号:6171401
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项目类别:
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资助金额:$24.36万
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财政年份:1997
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负责人:WILLIAM B. RIZZO
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依托单位:
Ichthyosis in Sjogren-Larsson syndrome
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批准号:7196136
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项目类别:
-
资助金额:$33.51万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
-
依托单位:
Ichthyosis in Sjogren-Larsson Syndrome
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批准号:6641987
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项目类别:
-
资助金额:$34.91万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
ICHTHYOSIS IN SJOGREN/LARSSON SYNDROME
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批准号:2006982
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项目类别:
-
资助金额:$23.86万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
Ichthyosis in Sjogren-Larsson Syndrome
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批准号:6847859
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项目类别:
-
资助金额:$35.61万
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财政年份:1997
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负责人:WILLIAM B. RIZZO
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依托单位:
Ichthyosis in Sjogren-Larsson Syndrome
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批准号:6923233
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项目类别:
-
资助金额:$0.7万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
Ichthyosis in Sjogren-Larsson Syndrome
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批准号:6328312
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项目类别:
-
资助金额:$34.44万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
ICHTHYOSIS IN SJOGREN/LARSSON SYNDROME
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批准号:2683356
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项目类别:
-
资助金额:$22.61万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
-
依托单位:
Ichthyosis in Sjogren-Larsson Syndrome
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批准号:6511889
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项目类别:
-
资助金额:$8.61万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
Ichthyosis in Sjogren-Larsson syndrome
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批准号:7288831
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项目类别:
-
资助金额:$33.24万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
-
依托单位:
Ichthyosis in Sjogren-Larsson Syndrome
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批准号:7477796
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项目类别:
-
资助金额:$32.2万
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财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
PHENOTYPE VARIATION IN SJOGREN LARSSON
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批准号:6246026
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项目类别:
-
资助金额:$2.76万
-
财政年份:1997
-
负责人:WILLIAM B. RIZZO
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依托单位:
海外基金