MITOFUSIN AGONISTS TO TREAT NEURODEGENERATIVE DISEASE
MITOFUSIN AGONISTS TO TREAT NEURODEGENERATIVE DISEASE
批准号:
10290982
负责人:
Gerald W. Dorn
金额:
$7.85万
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:
2021-03-15 至 2021-07-31
关键词:
AffectAgonistAmericanAmyotrophic Lateral SclerosisBiotechnologyCaregiversCellsCessation of lifeCharcot-Marie-Tooth DiseaseDataDiseaseDisease OutcomeDisease ProgressionDrug KineticsFDA approvedFamilyFeasibility StudiesFutureGeneticGenetic RiskHealthcareHuntington DiseaseIndividualInterventionInvestigationLeadManufactured BaseballMetabolismMitochondriaModelingMorbidity - disease rateMotionMuscle WeaknessMuscular AtrophyMutationNeurodegenerative DisordersOther GeneticsParalysedPatientsPeripheral Nervous System DiseasesPharmaceutical PreparationsPhasePopulationPropertyProteinsPublishingRare DiseasesSmall Business Technology Transfer ResearchUniversitiesValidationWashingtonblood-brain barrier penetrationeffective therapyfirst-in-humanhumanized mouseimprovedin vivomedical schoolsmitochondrial dysfunctionmitochondrial fitnessmortalitymouse modelnovel drug classpre-clinicalresponse to injurysmall moleculetraffickingvalidation studies
中文摘要
治疗神经退行性疾病的丝裂酶激动剂
英文摘要
Mitofusin agonists for the treatment of neurodegenerative diseases
Gerald W Dorn II, MD
Mitochondria in Motion, Inc.
Washington University in St Louis School of Medicine
Abstract: There are a number of rare neurodegenerative diseases, including Amyotrophic Lateral
Sclerosis (ALS) and Huntington’s Disease (HD), for which there is no available or effective therapy
and which lead to significant morbidity and mortality in affected populations. Mitochondria in Motion,
Inc. will develop and produce investigational first-in-class small molecule mitofusin agonists, under an
FDA approved IND, to treat these conditions. Mitofusin agonists enhance mitochondrial fitness,
metabolism, and trafficking within cells, thus improving homeostatic functioning and injury-responses
of cells adversely impacted by genetic mitochondrial dysfunction. Our published disease focus for
mitofusin agonists was Charcot-Marie-Tooth disease type 2A, caused by mutations in our drug’s
protein target, Mitofusin 2. Here, we hypothesized that intervention with a mitofusin agonist would
have beneficial effects on other genetic peripheral neuropathies with a mitochondrial component,
which is supported by our preclinical data in ALS and HD patient-derived cells. Thus, we will fill
an unmet healthcare need and build a commercial enterprise to serve the ~20,000 Americans with
ALS and the ~150,000 Americans suffering from or at genetic risk for developing HD, their caregivers
and families. In this Phase I STTR we propose to optimize the pharmacokinetic properties of
mitofusin agonists for systemic administration and blood-brain-barrier penetration (Aim 1), and
complete in vivo feasibility and validation studies of mitofusin agonists to delay disease progression in
the well characterized SOD1G93A mouse model of ALS. Our deliverable in Phase I will be a
mitofusin agonist(s) ready for STTR Phase II IND-enabling studies and validation in an expanded
number of orphan diseases, to prepare for future first-in-human trials.
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Mitofusin Agonists to Treat Neurodegenerative Disease
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批准号:10383118
-
项目类别:
-
资助金额:$96.87万
-
财政年份:2022
-
负责人:Gerald W. Dorn
-
依托单位:
Mitofusin Agonists to Treat Neurodegenerative Disease
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批准号:10618385
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项目类别:
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资助金额:$98.62万
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财政年份:2022
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负责人:Gerald W. Dorn
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依托单位:
MITOFUSIN AGONISTS TO TREAT NEURODEGENERATIVE DISEASE
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批准号:10020801
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项目类别:
-
资助金额:$22.47万
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财政年份:2019
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负责人:Gerald W. Dorn
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依托单位:
Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A
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批准号:10471364
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项目类别:
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资助金额:$90.18万
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财政年份:2019
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负责人:Gerald W. Dorn
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依托单位:
Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A
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批准号:9901962
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项目类别:
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资助金额:$25.44万
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财政年份:2019
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负责人:Gerald W. Dorn
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依托单位:
Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A
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批准号:10253340
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项目类别:
-
资助金额:$105.92万
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财政年份:2019
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负责人:Gerald W. Dorn
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依托单位:
THE MITOCHONDRIAL DYNAMISM/FITNESS/BIOGENESIS INTERACTOME IN CARDIAC DISEASE
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批准号:10530619
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项目类别:
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资助金额:$91.5万
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财政年份:2017
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负责人:Gerald W. Dorn
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依托单位:
THE MITOCHONDRIAL DYNAMISM/FITNESS/BIOGENESIS INTERACTOME IN CARDIAC DISEASE
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批准号:10321894
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项目类别:
-
资助金额:$91.5万
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财政年份:2017
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负责人:Gerald W. Dorn
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依托单位:
MOLECULAR ORCHESTRATION OF MITOCHONDRIAL FITNESS VIA REPLACEMENT OR REPAIR
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批准号:9101442
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项目类别:
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资助金额:$38.13万
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财政年份:2016
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负责人:Gerald W. Dorn
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依托单位:
Linking cell death and mitochondrial quality control mechanisms in heart disease
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批准号:9032529
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项目类别:
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资助金额:$51.5万
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财政年份:2015
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负责人:Gerald W. Dorn
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依托单位:
Linking cell death and mitochondrial quality control mechanisms in heart disease
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批准号:9172493
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项目类别:
-
资助金额:$26.8万
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财政年份:2015
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负责人:Gerald W. Dorn
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依托单位:
Linking cell death and mitochondrial quality control mechanisms in heart disease
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批准号:9223745
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项目类别:
-
资助金额:$51.06万
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财政年份:2015
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负责人:Gerald W. Dorn
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依托单位:
MICRORNA TARGETING IN HEART FAILURE
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批准号:8238967
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项目类别:
-
资助金额:$38.0万
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财政年份:2011
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负责人:Gerald W. Dorn
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依托单位:
MICRORNA TARGETING IN HEART FAILURE
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批准号:8774629
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项目类别:
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资助金额:$37.43万
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财政年份:2011
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负责人:Gerald W. Dorn
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依托单位:
MITOCHONDRIAL MANIPULATION AND ANALYSIS IN DROSOPHILA HEARTS
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批准号:8309022
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项目类别:
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资助金额:$19.0万
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财政年份:2011
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负责人:Gerald W. Dorn
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依托单位:
MITOCHONDRIAL MANIPULATION AND ANALYSIS IN DROSOPHILA HEARTS
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批准号:8190154
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项目类别:
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资助金额:$22.8万
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财政年份:2011
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负责人:Gerald W. Dorn
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依托单位:
MICRORNA TARGETING IN HEART FAILURE
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批准号:8399037
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项目类别:
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资助金额:$36.18万
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财政年份:2011
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负责人:Gerald W. Dorn
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依托单位:
MICRORNA TARGETING IN HEART FAILURE
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批准号:8588991
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项目类别:
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资助金额:$37.24万
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财政年份:2011
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负责人:Gerald W. Dorn
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依托单位:
CTRIP: Genetic Testing to Individualize Management of Common Heart Diseases
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批准号:7853706
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项目类别:
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资助金额:$96.11万
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财政年份:2009
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负责人:Gerald W. Dorn
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依托单位:
CTRIP: Genetic Testing to Individualize Management of Common Heart Diseases
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批准号:7939777
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项目类别:
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资助金额:$94.39万
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财政年份:2009
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负责人:Gerald W. Dorn
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依托单位:
国内基金
海外基金
Agonist-GPR119-Gs复合物的结构生物学研究
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批准号:32000851
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项目类别:青年科学基金项目
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资助金额:24.0万元
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批准年份:2020
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负责人:乔安娜
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依托单位: