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AD R esearch Update

AD R esearch Update. Steven H. Ferris, PhD Friedman Professor and Director NYU Alzheimer’s Disease Center Silberstein Alzheimer’s Institute Center for Cognitive Neurology. Combining Two Important Developments. Potential for very early detection of AD

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AD R esearch Update

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  1. AD Research Update Steven H. Ferris, PhD Friedman Professor and Director NYU Alzheimer’s Disease Center Silberstein Alzheimer’s Institute Center for Cognitive Neurology

  2. Combining Two Important Developments • Potential for veryearly detection of AD • “Preclinical AD”: Very early pathology in brain, no clinical symptoms (5-15 years) • Amyloid Tau/Synaptic loss Subtle impairment • Development and clinical testing of “disease modifying” treatments to slow progression • e.g., anti-amyloid, anti-tau compounds, other neuroprotective agents

  3. National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Alzheimer's Disease: Criteria for preclinical Alzheimer’s Disease (Sperling et al., 2011 (Adapted from Jack et al., 2010) What is available for early detection? • Biomarkers: Great potential for very early detection of AD • However… • Invasive • Costly • EBAD Study New cognitive tests for early detection

  4. Current NYU Research on Preclinical Detection of AD • Center for Brain Health (CBH) biomarker studies • CSF studies: β-amyloid and P-Tau • Neuroimaging: MRI, PET-amyloid, PET-tau • EBAD Study: Early cognitive detection of AD • Normal elderly receive sensitive cognitive battery • Validation using PET-amyloid, MRI (and CSF Aβ and tau)

  5. AD Treatment Targets Amyloid Precursor Protein Secretase Inhibitors Selective Ab lowering agents Amyloid b monomer Anti-aggregation Anti-fibril Amyloid boligomers Passive Immunization Active Immunization • Amyloid Plaques • NFTs (tau) • Inflammation • Oxidative stress Antioxidants Anti-inflammatory agents Anti-tau aggregation/phosphorylation Symptomatic Drugs Anti-cholinesterases; NMDA antagonists Nicotinic agonists, memory enhancers Neuronal loss, neurotransmitter loss, cognitive deficit

  6. Immunotherapy Strategies • Passive immunity: • Bapineuzumab(Janssen AI): Monoclonal antibodies; Phase III trials in AD: No clinical benefits • Solanezumab (Lilly): Monoclonal Antibodies; Phase III trials in AD: Possible benefit--only in mild AD • Gammagard[IVIG] (Baxter/ADCS): Human Aß antibodies; Phase III trial in AD: No clinical benefits • Other antibodies: Genentech/Roche, Eisai, Biogen • Active “vaccines” • Aß fragments (Janssen AI, Pfizer, others; Phase I-II)

  7. Other Anti-Amyloid Strategies • γ-Secretase inhibitors/modulators • Semagacestat (Lilly): Phase III in AD halted, No clinical benefits • BMS-708163 (BMS):Phase II in AD and MCI, No clinical benefits • ß-Secretase (BACE) inhibitors • MK8931 (Merck): Phase II in AD; Prodromal AD • E2609 (Eisai): Phase I in AD

  8. Conclusions • Major advances in early detection can identify presymptomatic AD • Important clinical trials of disease modifying agentsthat mayslow progression (amyloid, tau, other neuroprotective targets) • Pre-symptomatic detection coupled with effective disease slowing agents will facilitate future prevention

  9. Clinical Trials at NYU • BACE Inhibitor (MK-8931) ↓ amyloid production; Phase IIb, oral, AD and prodromal AD (MCI) • TMS + Cognitive Remediation: Brain stimulation + cognitive training in AD(weekdays, 6-weeks) • Ketonergic metabolism (Axona):  brain metabolism • Insulin sensitizer-Pioglitazone (Takeda): 5-year prevention trial; normal elderly with genetic risk for AD • Amyloid antibody-BAN2401 (Eisai): MCI and mild AD ----------------------------------------------------------------------------------------------------------- • Intranasal Insulin (ADCS): MCI and mild AD • A4 trial of Solanezamab(ADCS): Prevention in preclinical AD • Solanezamab in mild AD: Confirmation of prior results • 14861B (Lundbeck): Mild-moderate AD • Anti-tau compound-T-817(ADCS/Toyama): Mild-moderate AD • Crenezumab (Genentech): Mild-moderate AD; Prodromal AD (MCI) • Nicotinic agonist (EnVivo): Mild-moderate AD

  10. NYU Alzheimer’s Disease CenterSilberstein Alzheimer’s InstituteCenter on Cognitive Neurology Clinical Trials: 212-263-5708 ADC Participation: 212-263-8088 Center for Brain Health: 212-263-7563 Barlow Center: 212-263-3210

  11. Thank you Please complete the Post-Test located on the yellow form in your folders, and the feedback survey located on the pink form. If you would like to be contacted with more information from NYU Alzheimer’s Disease Center, please also complete the reverse side of the yellow form.

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