2018
Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models
Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, Baeriswyl JL, Cavegn N, Senn L, Su L, Marsh G, Auluck P, Montrasio F, Nitsch RM, Hirst WD, Cedarbaum JM, Pepinsky R, Grimm J, Weinreb PH. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models. Neurobiology Of Disease 2018, 124: 276-288. PMID: 30381260, DOI: 10.1016/j.nbd.2018.10.016.Peer-Reviewed Original ResearchConceptsΑ-Syn pathologyParkinson's diseaseΑ-synDisease progressionMouse modelPrevention of PDPhase 2 clinical trialPD mouse modelPD brain tissueDisease modelsDopamine transporter densityParkinson's disease modelΑ-synuclein antibodyPromising therapeutic approachDifferent mouse modelsHealthy elderly individualsΑ-syn fibrilsEpitope mapping studiesDopaminergic terminalsRecombinant α-synPreclinical dataClinical trialsTherapeutic approachesMotor impairmentElderly individuals
2015
Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H, Thein S, Shiovitz T, Pilcher G, Ferris S, Colby S, Kerselaers W, Dockens R, Soares H, Kaplita S, Luo F, Pachai C, Bracoud L, Mintun M, Grill JD, Marek K, Seibyl J, Cedarbaum JM, Albright C, Feldman HH, Berman RM. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA Neurology 2015, 72: 1324-1333. PMID: 26414022, DOI: 10.1001/jamaneurol.2015.0607.Peer-Reviewed Original ResearchConceptsNonmelanoma skin cancerObservational cohortProdromal Alzheimer's diseaseProdromal ADClinical trialsPositron emission tomographyAlzheimer's diseaseDiscontinuation ratesCSF biomarkersBiomarker criteriaTreatment phasePlacebo-controlled phase 2 clinical trialSkin cancerGastrointestinal tract adverse eventsKey clinical outcome measuresSerious adverse event ratesΓ-Secretase Inhibitor AvagacestatEmission tomographyPhase 2 clinical trialPotential disease-modifying agentsBrain atrophy ratesLow discontinuation rateAdverse event ratesDisease-modifying agentsGreater brain atrophy