Lead Innovator: Jaime Grutzendler, MD

IP: Patents Pending

Related: OCR8237

Pathological Neuronal Branching: Plaque-Associated Axonal Spheroids (PAAS)

• Axon Conduction Disorders
  • Alzheimer's Disease
  • Other diseases of nerve conduction
• Standard of Care: None
• Novelty: no drugs target PAAS
• In Vivo Model: mouse model recapitulates PAAS pathology of human post-mortem brain samples (Fig. 1)
• Axonal Spheroid-enriched Targets
  • Target 1: endolysosomal resident enzyme
  • Target 2: plasma membrane integral protein
• Intervention Strategies: small molecules, siRNA/antisense, antibody, PROTACS
• In Vivo Assessment of Efficacy: brain interhemispheric axonal conduction

Validity of Therapeutic Hypothesis

• Human/Mouse: human and mouse PAAS morphology (Fig.1)
• Mouse: diminished PAAS (observed) results in normalization of axonal conductance (two targets, two modalities; Fig.2a: Target 1/ Fig.2b:Target 2)

Anticipated Clinical Assessment of Efficacy of PAAS-directed Therapy

• Neuropsychological and computer-assisted measurements of cognitive processing speed/reaction times.