Further Preclinical Development of a Bio‐therapeutic Against Porphyromonas gingivalis for the control of Systemic and Neuro‐inflammation related Dementia and Alzheimer’s Disease

Abstract

Addressing novel mechanisms and effective therapeutic treatments for cognitive decline, Dementia and Alzheimer’s Disease is a major public health need. Keystone Bio have identified that specific virulent strains of Porphyromonas gingivalis (Pg) and the release of specific virulence factors/toxins in the oral cavity as the primary driver/causation of systemic/neuro‐vascular inflammation/degenerative diseases i.e., cognitive decline/dementias/Alzheimer’s disease (Nara et. al 2021). A recent landmark finding was reported in a sub‐cohort analysis from a Phase 2/3 GAIN trial (n = 238) demonstrated that lowering the load of Pg in the mouth leads to a significant improvement of cognitive slowing at both 24 and 48 weeks in participants with mild to moderate AD. Another study showed lowering the load of Pg in the mouth had a favorable effect on AD‐related brain atrophy (https://doi.org/10.1002/alz.12378). Pg OMVs and systemic system diseases has many well‐defined examples such as: cardiometabolic diseases‐ Pg OMVs attenuate insulin induced Akt/GSK‐3_ signaling in hepatic HepG2 cells, thereby causing changes in glucose metabolism in the liver and promoting the development of diabetes and increase vascular permeability by cleaving endothelial cell connexins such as PECAM‐1, thereby promoting cardiovascular diseases.

Keystone Bio has further developed both a companion diagnostic (CDx) and a clinical, proof‐of‐concept tested, first generation, safe, efficacious, precision, bio‐therapeutic murine monoclonal antibody (KB‐001) for the diagnosis, treatment and monitoring against the oral bacteria and major virulent factor/toxin of Pg. The antibody engagement is with the later stages of the complex virulent factor/toxin secretion containing outer membrane vesicles from the bacteria thereby interfering/stopping all necessary metabolic, host defense, energy‐producing sources, adherence and biofilm formation and integrity (Nara et. al 2021). The talk will review what now seems like a solid case for causation in the role of virulent/toxin secreting strains of in neuro‐inflammation leading to cognitive decline, dementia, Sporadic Alzheimer’s disease and possibly Parkinson’s.