2024
Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease
Feldman H, Messer K, Qiu Y, Sabbagh M, Galasko D, Turner R, Lopez O, Smith A, Durant J, Lupo J, Revta C, Balasubramanian A, Kuehn-Wache K, Wassmann T, Schell-Mader S, Jacobs D, Salmon D, Léger G, DeMarco M, Weber F, Group F. Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease. Journal Of Alzheimer's Disease 2024, 101: s79-s93. PMID: 39422941, PMCID: PMC11494639, DOI: 10.3233/jad-231126.Peer-Reviewed Original ResearchConceptsGlutaminyl cyclasePost-translationallyAlzheimer's diseasePhase 2bEarly phase clinical trialsAmyloid-bCytokine monocyte chemoattractant protein-1Monocyte chemoattractant protein-1Highest tolerated doseLonger-term safetyPhase clinical trialsWeeks of treatmentFirst-in-classTarget of therapyUnique dual mechanismChemoattractant protein-1Interim futility analysisClinical efficacyDisease cascadeProtein 1Electroencephalogram changesOptimal doseClinical trialsAnalysis of cognitive functionHigh dosesA framework for translating tauopathy therapeutics: Drug discovery to clinical trials
Feldman H, Cummings J, Boxer A, Staffaroni A, Knopman D, Rizzo S, Territo P, Arnold S, Ballard C, Beher D, Boeve B, Dacks P, Diaz K, Ewen C, Fiske B, Gonzalez M, Harris G, Hoffman B, Martinez T, McDade E, Nisenbaum L, Palma J, Quintana M, Rabinovici G, Rohrer J, Rosen H, Troyer M, Kim D, Tanzi R, Zetterberg H, Ziogas N, May P, Rommel A. A framework for translating tauopathy therapeutics: Drug discovery to clinical trials. Alzheimer's & Dementia 2024 PMID: 39316411, DOI: 10.1002/alz.14250.Peer-Reviewed Original ResearchPrimary tauopathiesClinically heterogeneous neurodegenerative diseasesTau protein aggregationHeterogeneous neurodegenerative diseaseSurrogate disease biomarkersTauopathiesProtein aggregationDefinition of rare diseasesAlzheimer's diseaseNeurodegenerative diseasesClinical trialsEarly-phase clinical trialsEarly-phase trialsDisease biomarkersFrontotemporal degenerationDrug developmentProgressive supranuclear palsyDiscovery to clinical trialsSelection of targetsTherapeuticsPharmacodynamic biomarkersA multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease
Galasko D, Farlow M, Lucey B, Honig L, Elbert D, Bateman R, Momper J, Thomas R, Rissman R, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman H. A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease. Alzheimer's Research & Therapy 2024, 16: 151. PMID: 38970127, PMCID: PMC11225352, DOI: 10.1186/s13195-024-01490-z.Peer-Reviewed Original ResearchConceptsOrally administered small moleculeFractional synthesis rateAscending dose studyDose-dependent loweringIRB-approved protocolEarly ADMini-Mental State ExamDose-dependent effectAlzheimer's diseaseBlood patchDouble-blindWell-toleratedCatheter placementPreclinical modelsLumbar punctureDose studyIntravenous infusionMild cognitive impairmentEvaluate safetyPlacebo participantsCognitive measuresStable isotope labeling kineticsActive drugClinical trialsADAS-Cog12Asian Cohort for Alzheimer Disease (ACAD) Pilot Study
Peavy G, Võ N, Revta C, Lu A, Lupo J, Nam P, Nguyễn K, Wang L, Feldman H. Asian Cohort for Alzheimer Disease (ACAD) Pilot Study. Alzheimer Disease & Associated Disorders 2024, 38: 277-284. PMID: 39177172, PMCID: PMC11340683, DOI: 10.1097/wad.0000000000000631.Peer-Reviewed Original ResearchConceptsSubjective cognitive complaintsOlder Vietnamese AmericansVascular risk factorsMild cognitive impairmentVietnamese AmericansRisk factorsMeasuring subjective cognitive complaintsPilot studyCommunity advisory boardNongenetic risk factorsCommunity-based researchAD risk factorsAlzheimer's diseaseDepressive symptomsConsensus teamCognitive complaintsBilingual/bicultural staffAD riskAssessment toolAdvisory boardVietnamese communityExploratory analysisCognitive difficultiesCognitive impairmentParticipantsPharmacoepidemiology evaluation of bumetanide as a potential candidate for drug repurposing for Alzheimer's disease
Morales J, Gabriel N, Natarajan L, LaCroix A, Shadyab A, Xu R, Silverman J, Feldman H, Hernandez I, Aslanyan V, Bang A, Bevins E, Bowman G, Boyarko B, Chen X, Clelland C, Dodge H, Durant J, Edland S, Evans A, Galasko D, Gerwick W, Greenberg B, Herman M, Herold T, Hook V, Jacobs D, Kaye J, Kim D, Koo E, Kosik K, Léger G, Lupo J, Messer K, Momper J, Nygaard H, Pa J, Quinti L, Revta C, Rexach J, Rizzo S, Rynearson K, Schneider L, Slusher B, Tanzi R, Territo P, Yokoyama J. Pharmacoepidemiology evaluation of bumetanide as a potential candidate for drug repurposing for Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 5236-5246. PMID: 39030734, PMCID: PMC11350022, DOI: 10.1002/alz.13872.Peer-Reviewed Original ResearchRisk of ADCross-sectional analysis of electronic health recordsAnalysis of electronic health recordsAD riskAssociated with risk of ADAssociated with AD riskAssociated with decreased prevalenceElectronic health recordsRetrospective cohort study designMedicare claims dataCohort study designCox proportional hazards regressionAssociated with riskCross-sectional analysisProportional hazards regressionPrevalence of ADMultiple sensitivity analysesAlzheimer's diseaseHealth recordsMedicare beneficiariesMedicare dataClaims dataStudy designHazards regressionPatient characteristicsProtocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam)
Feldman H, Luchsinger J, Léger G, Taylor C, Jacobs D, Salmon D, Edland S, Messer K, Revta C, Flowers S, Jones K, Koulman A, Yarasheski K, Verghese P, Venkatesh V, Zetterberg H, Durant J, Lupo J, Gibson G, Group F. Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer’s disease (BenfoTeam). PLOS ONE 2024, 19: e0302998. PMID: 38809849, PMCID: PMC11135745, DOI: 10.1371/journal.pone.0302998.Peer-Reviewed Original ResearchConceptsPhase 2bPhase 2aRandomized double-blind placebo-controlled trialDouble-blind placebo-controlled trialCo-primary efficacy endpointsTolerability eventsBest-tolerated dosePlacebo-controlled trialWell-tolerated dosesAlzheimer's diseaseLonger-term safetyEfficacy of drug deliveryWeeks of treatmentTargeted therapeutic approachesErythrocyte transketolase activityGroups of participantsDouble-blindPlacebo armEfficacy endpointSecondary endpointsOral treatmentPharmacokinetic measurementsClinical trialsTherapeutic approachesBlood markersPersonal value of Alzheimer's disease biomarker testing and result disclosure from the patient and care partner perspective
Patel K, Yang D, Feldman H, Hsiung G, Nygaard H, Best J, Dwosh E, Robillard J, DeMarco M. Personal value of Alzheimer's disease biomarker testing and result disclosure from the patient and care partner perspective. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2024, 10: e12463. PMID: 38596482, PMCID: PMC10999946, DOI: 10.1002/trc2.12463.Peer-Reviewed Original ResearchCare partnersSemi-structured phone interviewsCare partner perspectivesCare partners' experiencesPatients' decision-making processPre-test counsellingRoutine medical careBiomarker testingHealthy behaviorsCaregiving responsibilitiesPost-disclosureRoutine carePositive lifestyleLifestyle changesPhone interviewsMedical carePartners' experiencesCarePartner's perspectiveMedical interventionsAlzheimer's diseaseObservational studyClinic patientsStudy findingsPositive feelings
2023
Prognostic value of plasma biomarkers in a clinical trial of mild‐to‐moderate Alzheimer’s Disease
Qiu Y, Messer K, Jacobs D, Salmon D, Kaplita S, Wellington C, Stukas S, Askew B, Brewer J, Brody M, Donahue L, Drake J, Grossman K, Hendrix S, Jicha G, Leger G, Porsteinsson A, Shadyab A, Taylor C, Thomas R, van Dyck C, Zhang J, Coric V, Qureshi I, Feldman H, Group A. Prognostic value of plasma biomarkers in a clinical trial of mild‐to‐moderate Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.076047.Peer-Reviewed Original ResearchModerate Alzheimer's diseaseAlzheimer's Disease Cooperative StudyPlasma NfLPlasma biomarkersCDR-SBADAS-cog11Baseline NfLAlzheimer's diseaseMRI outcomesClinical trialsTrial designBaseline biomarker measurementsBaseline plasma biomarkersPlacebo-controlled RCTsClinical trial designOnly significant associationGlobal functionClinical declineClinical outcomesP-tauTotal tauTreatment armsPrognostic valueSignificant treatment effectBiomarker changes
2016
Role of INPP5D, PTK2B, ZCWPW1 and TREM 2 in Predicting Risk of Progression in Cognitively Impaired Subjects to Alzheimer's Disease (P5.166)
Hawkins C, Fok A, Feldman H, Sadovnick D, Hsiung G. Role of INPP5D, PTK2B, ZCWPW1 and TREM 2 in Predicting Risk of Progression in Cognitively Impaired Subjects to Alzheimer's Disease (P5.166). Neurology 2016, 86 DOI: 10.1212/wnl.86.16_supplement.p5.166.Peer-Reviewed Original Research
2013
Contribution of Genetic Risk Factors in Progression from Cognitive Impairment to Alzheimer Disease in 2 Large Canadian Cohorts (S34.001)
Omoumi A, Fok A, Feldman H, Sadovnick D, Hsiung G. Contribution of Genetic Risk Factors in Progression from Cognitive Impairment to Alzheimer Disease in 2 Large Canadian Cohorts (S34.001). Neurology 2013, 80 DOI: 10.1212/wnl.80.7_supplement.s34.001.Peer-Reviewed Original Research