Single domain antibody development for improving vascular dysfunction in alzheimer's disease - alzheimer's disease (ad) is the most common form of neurodegenerative disorder associated with aging

The National Institute on Aging awarded Aivocode, Inc. a Phase II Project Grant of $3.727 million on September 20, 2025, under the Aging Research program (CFDA 93.866) to develop single domain antibodies targeting connective tissue growth factor (CTGF) for treating vascular dysfunction in Alzheimer's disease.

Aivocode will test single domain antibodies against CTGF to neutralize CTGF activity in transgenic mouse models of Alzheimer's disease, with the goal of improving vascular dysfunction and slowing disease progression. The work builds on preliminary research using in vivo phage display to identify CTGF as a therapeutic target present on brain vasculature in Alzheimer's models. Successful completion will yield a lead single domain antibody candidate suitable for further drug development.

Performance occurs in San Diego, California. The award period extends from September 20, 2025 through May 31, 2027.

One of the hallmarks of this disorder is the progressive loss of neuronal cells, which ultimately becomes fatal. Several lines of investigations characterized by the loss of mural cells (PERICYTES) and compromised blood-brain-barrier, in pathogenesis of ad. Academic collaborators and founders of aivocode INC., the applicant company, have employed unbiased screening with in vivo phage display to probe specific vascular signature present in the brains of transgenic ad mice. This new approach to ad studies has generated a new and understudied therapeutic target, connective tissue growth factor (CTGF). CTGF binds extracellular matrices and cell surfaces including brain vasculature in ad mice and can stimulate endothelial cell migration and angiogenesis. Our preliminary data suggests that CTGF plays a role in causing abnormalities in ad brain vessels and can potentially be a new therapeutic target for ad drug development. In this phase II application, we propose to test single domain antibodies against CTGF to neutralize CTGF activity in mouse models of ad to improve vascular dysfunction and test if IT leads to slower disease progression. The results of this study will provide a lead single domain antibody as a drug candidate for further development for ad.