Day Two


Thursday, June 23, 2022 | 9.00 AM - 3.00 PM (EST)

9:00 am Online Registration

9:20 am Chair’s Opening Remarks

Leveraging Disease Modelling & Efficacy Proof to Enhance Preclinical Efforts

9:30 am Reinventing Drug Discovery for Rare CNS Genetic Diseases


  • Leveraging patient-derived organoid models of human brain disease, scaled biology, and machine learning to drive CNS drug discovery
  • Utilizing patient-derived organoids to elucidate disease pathophysiology; to formulate key therapeutic hypotheses; and to identify and validate drug targets, cellular assays and biomarkers to guide clinical candidate selection
  • Advantages of human-first proof of efficacy obtained from brain organoid models for clinical translation

10:00 am AAV Gene Therapy for the Treatment of Autosomal Dominant Alzheimer’s Disease


  • The role of presenilin in ADAD and rationale for a gene replacement approach
  • Preclinical proof-of-principle data in mouse models and human-derived ADAD mutation-bearing cell lines
  • Evaluating expression and biodistribution in nonhuman primates
  • Discussing phase 1/2 clinical trial plans

10:30 am Morning Break & Networking

Understanding Disease History & Preclinical Packages

11:00 am Utilizing Natural History Data for Identifying Best Clinical Outcomes


  • Access to Natural History data from longitudinal studies increases our knowledge of rare and genetic neurodegenerative disease onset and progression
  • Involvement of people living with rare & genetic neurodegenerative disease or their carer is key to selecting most meaningful symptoms
  • Development of new clinical outcomes requires early collaboration between academics, pharma and regulators but remains very challenging at prodromal/early stage of the disease with absence or low functional impact

11:30 am Making Bench to Bedside a Reality & not just a Catch Phrase


  • Seduction of the P1 Mouse: Using Models Wisely and Appropriately
  • Crossing the Valley of Death: What can (and can’t) preclinical studies do to help inform and prepare for clinical studies

12:00 pm Lunch & Networking

Human Genetics – What it Teaches us About Rare Diseases

1:00 pm Therapeutic Targeting of Iron-Driven Neurodegeneration by Ferroptosis


  • Leveraging rare diseases, including Neurodegeneration with Brain Iron Accumulation (NBIA), point to iron dysregulation as a causal factor in the neurodegenerative disease
  • Understanding that ferroptosis is a cause of iron-driven cell death that targets multiple brain cell types
  • Utilizing ferroptosis inhibition as a key therapeutic node in rare diseases characterized by brain iron accumulation

1:30 pm Diagnostic Testing in Patient Selection for Rare Disease in Clinical Trials

  • Yan Ni Executive Director, Biomarkers and Precision Medicine, Passage Bio


  • Diagnosing patients with rare disease
  • Complimenting mutation screening with a second-tier diagnostic testing

2:00 pm AAV-DNase I Delivery Targeting Extracellular DNA as a New Strategy for Treatment of Alzheimer’s Disease

  • George Tetz Chief Executive Officer, Human Microbiology Institute


  • Extracellular DNA from different bacterial species can act as a virulence factor triggering prion-like aggregation
  • Bacterial DNA can participate in the cross-kingdom protein misfolding, leading to the aggregation of tau and beta-amyloid proteins.
  • Extracellular DNA as a new therapeutic target for the treatment of neurodegenerative diseases.

2:30 pm Developing Gene Therapies for Neurological Disorders

  • Lingzhi Zhao Senior Director - Gene Therapy & Transnational Discovery Gene Therapy, AGTC


  • Understanding how to conduct a gene therapy trial in rare diseases
  • Developing novel formulations for gene therapy which show promise in their ability to increase the concentration and stability of the gene therapy while reducing unwanted effects for the patient

3:00 pm Chair’s Closing Remarks & Close of Summit