VDP-153 [Funding] Project Ab4AD: Identifying Protective Antibodies Against Alzheimer's Disease

One-liner

Project Ab4AD aims to identify antibodies that protect against Alzheimer's Disease (AD) by examining immune responses to specific pathogens, with the goal of developing early diagnostic tools and preventive therapies.

Team

Principal Investigator: Dr. Daniel Bar Project Managers: Ella McCarthy-Page, Aidin Kazemizadeh, David Falvo, Logan Bishop-Currey, Benji Leibowitz Sourcer: Lutz Kummer Key Researchers and Collaborators: Dr. Omer Bender, Dr. Naor Sagy

Simple Summary

Project Ab4AD focuses on identifying antibodies in elderly individuals without dementia that protect against Alzheimer's Disease. By comparing these immune responses to those of AD patients, the project aims to develop diagnostic tools and therapies that can predict and prevent AD, offering new hope for millions of people and their families. Problem Alzheimer's Disease (AD) is a neurodegenerative disease responsible for 60–70% of dementia cases, characterized by amyloid β plaques, neurofibrillary tangles, and sustained inflammation. The "pathogen/infection hypothesis" suggests chronic infections may trigger sporadic AD onset. Evidence supports the involvement of pathogens like Porphyromonas gingivalis, Herpes Simplex Virus 1, and Chlamydia pneumoniae in AD. While exposure to these pathogens is common, only some individuals develop AD, suggesting specific immune responses may modulate disease risk.

Solution

Project Ab4AD proposes to:

Screen saliva and blood samples from non-demented elderly for antibodies against AD-linked pathogens. Use complete human proteomics to identify auto-antibodies for brain proteins. Compare immune responses of No-AD, AD patients, and younger controls to various pathogens. Identify pathogenic proteins recognized by each group's immune system and find significant differences.

Goals

Identify protective antibodies against AD Build a predictive model of immune-dependent AD-avoidance Provide an early diagnostic tool Establish a path toward vaccine development

Opportunity

Unmet Clinical Need Current AD treatments focus on symptom management rather than addressing underlying causes. There's a critical need for therapies that can prevent or slow disease progression. Market Potential The global Alzheimer's disease treatment market was valued at $4.9 billion in 2020, projected to reach $13.7 billion by 2027. Vision and Long-Term Objectives

Develop early diagnostic tools Create preventive and therapeutic solutions Establish predictive models Advance understanding of AD pathogenesis

Expected Outcomes

Identification of protective antibodies Development of predictive models Creation of early diagnostic tools Therapeutic development

Relevance to Longevity

This project addresses key aspects of aging and age-related diseases:

Targets altered intercellular communication Mitigates effects of chronic inflammation and infections on brain health Seeks to understand protection against dementia despite chronic infection Contributes to extending healthspan and lifespan

IP Roadmap

Kit for AD risk identification Antibodies for AD treatment Targets for AD vaccine

Experimental Plan

We will identify a differential immune response to AD-associated pathogens between AD, Non-AD and C individuals (aim 1), identify a differential immune response to human brain proteins (aim 2) and validate our findings using independent methods (aim 3). A successful completion of these aims would support the hypothesis that a specific immune response modulates the risk of developing AD. It will also enable a testable, quick and cost-effective way to validate these findings on different cohorts, both by us and by others.

Budget and Costs

This proposal requests $50k (27% of total budget) from VitaDAO. Remaining funding will come from other sources. Licensing terms are not yet finalized. If terms are not agreed upon, funding will be returned.

Budget

This proposal will allocate $50k (in ETH) from the $100k allocated to Catalyst projects in VDP-147. Senior Review Digest - Quantitative Average scores from three reviewers (out of 5):

Team Expertise: 3.0 Feasibility & Data: 2.7 Commercial Potential & Impact: 3.7 Novelty & Market Advantage: 2.7 IP Defensibility: 2.3 Relevance to Longevity: 5.0 General Conviction Score: 3.0

Majority view: This project is a moonshot. Recommendations: Two reviewers suggest follow-up, one recommends denial with feedback. Senior Review Digest - Qualitative

Reviewer 1

Would not endorse. Pros:

Limited AD diagnostics and treatments. New Dx or Tx would be beneficial. Cons: Lack of novelty in AD-infection link. Long timeline to diagnostic/treatment. Team lacks BD/Development experience.

Reviewer 2

Would endorse. Pros:

Focus on prevention rather than treatment. Experienced research team with preliminary data. Potential for new discoveries in AD-pathogen relationships. Cons: Early stage with unclear market analysis. Team may need additional partnerships. High-risk, high-reward project.

Reviewer 3

Would support if funding is used exclusively for antigen/antibody research. Pros:

Promising potential for early detection and vaccine. Team expertise in pathogen-related antigens/antibodies. Cons: Strategy focuses on early diagnosis tool. Lacks vaccine experts for long-term goals. Insufficient IP protection for diagnostic tool.