Matrix Metalloproteinase-2/-9 Inhibitor For The Treatment Of ALS
Matrix Metalloproteinase-2/-9 Inhibitor For The Treatment Of ALS
批准号:
9763774
负责人:
IRVING SUCHOLEIKI
金额:
$45.76万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-09-15 至 2021-01-31
关键词:
AddressAmyotrophic Lateral SclerosisAnimal ModelApplications GrantsAwardBehavioralBiochemicalBiologicalBiological AvailabilityBiological MarkersBody Weight decreasedCASP1 geneChemicalsClinicDeteriorationDevicesDiagnosisDiagnosticDiseaseDisease ProgressionDisease modelDoseDrug KineticsFDA approvedFemaleGelatinase AGelatinase BGoalsInvestigational New Drug ApplicationLabelLifeLife ExpectancyMeasuresMethodologyMorphologyMotor NeuronsMusNational Institute of Neurological Disorders and StrokeNervous system structureNeurodevelopmental DisorderOnset of illnessOralPenetrationPharmaceutical PreparationsPharmacologic SubstancePhaseProteinsRiluzoleRodent ModelRotarod Performance TestRunningSmall Business Innovation Research GrantSpinalTechnologyTestingTherapeuticTissuesWorkanimal efficacydiagnostic assaydosageefficacy studyefficacy testinginhibitor/antagonistmalemouse modelnervous system disordernovelpainful neuropathypre-clinicalresearch clinical testingresponsesuperoxide dismutase 1
中文摘要
项目概要/摘要。Aquilus Pharmaceuticals,Inc.建议评估一个
选择性,双重活性,基质金属蛋白酶-2(MMP-2)和MMP-9抑制剂,AQU-118,在
肌萎缩侧索硬化症(ALS)超氧化物歧化酶-1(SOD-1)小鼠模型。的目标
第一阶段是化学合成AQU-118,测定其在SOD-1中的口服药代动力学(PK),
小鼠,然后通过剂量反应确定其在ALS的SOD-1小鼠模型中的功效。最后,A
然后进行组织形态学和免疫组织化学研究,以确定是否或
与对照组相比,AQU-118的非口服给药导致脊髓组织内的任何生化变化
控制。所提出的工作的最终目标是评估是否双重活性MMP-2/-9
抑制剂可用于治疗ALS。
英文摘要
Project Summary/Abstract. Aquilus Pharmaceuticals, Inc. proposes to evaluate the effects of a
selective, dual active, matrix metalloproteinase-2 (MMP-2) and MMP-9 inhibitor, AQU-118, in the
superoxide dismutase-1 (SOD-1) mouse model of amyotrophic lateral sclerosis (ALS). The goals for
Phase I are to chemically synthesize AQU-118, determine its oral pharmacokinetics (PK) in SOD-1
mice and then determine its efficacy in the SOD-1 mouse model of ALS with dose response. Lastly, a
tissue morphology & immunohistochemical study will then be performed to determine whether or
not oral dosing with AQU-118 results in any biochemical changes within spinal tissues as compared
to controls. The ultimate goal of the proposed work is to evaluate whether a dual active MMP-2/-9
inhibitor can be used to treat ALS.
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