Groundbreaking Data Announced during Poster Presentations at Alzheimer’s Association International Conference 2021 and Being Published in Upcoming August Issue of Journal of Alzheimer’s Disease (currently in prepress)
ST. LOUIS–(BUSINESS WIRE)–Keystone Bio, a biotechnology company, is a frontrunner in developing precision biologics to eliminate Porphyromonas gingivalis (Pg), and is releasing groundbreaking data that shows bacterial toxic proteins from Pg in the mouth are released into the blood and cross the Blood Brain Barrier (BBB) as the major driver of sporadic Alzheimer’s and chronic inflammation. This new data supports a “Peripheral” model of P. gingivalis blood-transported toxic proteins delivered into the blood and brain versus the earlier literature in which human and animal model studies support the “local” gingipains Alzheimer’s Disease brain model. What this means for Alzheimer’s patients and those at early risk is that KB is developing a specific diagnostic and treatment to eliminate Porphyromonas gingivalis and the flow of these toxic proteins to the brain.
This data can now be integrated into a more unifying “Concept” and explanation for the “Infection Hypothesis” for Alzheimer’s Disease (AD) and other Dementia-related disease(s). A larger HagA Domain virulence factor is found in many AD and some aged matched control brain tissues. It’s complex role in local and systemic inflammatory diseases is well understood and further demonstrates systemic blood borne delivery for the bacterial source of “gingipains” in the brain.
This Groundbreaking Data was Presented in Three Posters this Week at the Alzheimer’s Association International Conference 2021.
- Porphyromonas gingivalis Outer Membrane Vesicles as the major drivers of and source for the toxic insult and iron accumulation/deposition in Alzheimer’s Disease. In this presentation, Keystone Bio features a hypothetical model of Porphyromonas gingivalis (Pg) and addresses if 1. either translocation to the brain from the oral cavity via blood lymphatics, intracellularly or via neuronal axoplasmic flow and establishing a productive infection of the brain leading to the local production and the accumulation of Pg exo-/endo-toxins (e.g. gingipains/LPS etc.) verses; or 2. the oral peripheral infection/colonization in the oral cavity shedding exo-/endo toxins and other virulence factors as either soluble forms or associated with complex actively secreted outer membrane vesicles (OMVs) into the blood and/or lymphatics and trans-migrating the neuro-vascular endothelium with entry into the neural parenchyma and its association with iron are important and notable differences in both pathogenesis of disease and the focus of treatment.
- Further Preclinical Development of an Clinically Effective Bio-therapeutic Against Porphyromonas gingivalis. In this presentation, Keystone Bio presents the ever increasing list of broad adverse medical conditions associated with Porphyromonas gingivalis (Pg) infection associated with the long term, oral, biofilm-associated colonization in humans leading to a state of chronic systemic inflammation with multiple organ system diseases (atherosclerosis, cardiovascular, stroke, diabetes type 2/metabolic syndrome, cancer, Alzheimer, etc.), stands in stark contrast to a grossly lacking set of effective treatments and/or prophylactic interventions. Using multiple technologies in microbiology, protein chemistry, proteomics, molecular biology, nucleic acid and protein sequencing, immunochemistry, scanning electron microscopy, biologics development, mid and large scale up hybridoma monoclonal antibody production and human chimeric antibody development and enzymology, an updated status of a newly developed precision biological will be presented.
- A Study on the Distribution of Porphyromonas gingivalis Repeated Epitope in Hemagglutinin/Adhesion and HagA gingipains Domain Antigen and DNA in Alzheimer brains. In this presentation, Keystone Bio focuses on specific bacterial infections and factors especially caused by the oral Keystone Pathogen-Porphyromonas gingivalis (Pg) in both humans and animal models have shown to initiate and chronically stimulate the systemic innate host defense systems and inflammasomes. Over time, these compromise the integrity of the blood brain barrier, localize in the brain parenchyma neurons and supporting cells and through multiple inflammatory pathways and lead to activation of microglia and astrocytes. A novel anti-pg bacterial monoclonal antibody currently in pre- and clinical development was used for all described work. Forty-six brain tissue samples (frontal and temporal biopsies) from 23 brain specimens (7 AD and 16 AMC) were subjected to PCR-based liquid hybridization assay to detect P. gingivalis DNA. All were negative for P. gingivalis DNA. Alzheimer brain sections from multiple functionally distinct anatomic regions and 15 different patient choroid plexus were tested by Porphyromonas gingivalis antigen-specific immuno-histochemistry.
Keystone Bio further Elaborates on this Groundbreaking Data in our Hypothesis Paper Being Published in the Upcoming August Issue of Journal of Alzheimer’s Disease (prepress currently available): Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease.
Abstract
Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced “chronic” multi-systems inflammatory disease(s) including Alzheimer’s disease (AD). It is possibly the only second identified unique example of a biological extremophile in the human body. Having a better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction are central to its future diagnosis, treatment, and possible prevention. The published literature around the role of Pg in AD highlights the bacteria’s direct role within the brain to cause disease. The available evidence, although somewhat adopted, does not fully support this as the major process. There are alternative pathogenic/virulence features associated with Pg that have been overlooked and may better explain the pathogenic processes found in the “infection hypothesis” of AD. A better explanation is offered here for the discrepancy in the relatively low amounts of “Pg bacteria” residing in the brain compared to the rather florid amounts and broad distribution of one or more of its major bacterial protein toxins. Related to this, the “Gingipains Hypothesis”, AD-related iron dyshomeostasis, and the early reduced salivary lactoferrin, along with the resurrection of the Cholinergic Hypothesis may now be integrated into one working model. The current paper suggests the highly evolved and developed Type IX secretory cargo system of Pg producing outer membrane vesicles may better explain the observed diseases. Thus it is hoped this paper can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment, and possible prevention.
Keystone Bio is Altering the Course of Disease through this Groundbreaking Science.
Keystone Bio is a clinical stage, biopharmaceutical company with novel disease-modifying, precision, anti-bacterial bio-therapeutics to target an important and largely unaddressed bacterial driver of systemic inflammation that significantly contribute to multiple inflammatory diseases such as heart disease and dementia/Alzheimer’s disease along with companion diagnostics to diagnose/identify people at risk and monitor treatment.
Using KB proprietary methods, KB has identified a bacterial toxic protein that is a primary driver of systemic inflammation. This bacterial toxic protein complex is secreted actively in large amounts by the bacteria for its own survival, however has off site systemic pathology in various end organs such as the brain in AD brain tissues. This virulent protein complex is packaged into distinct outer membrane vesicles, breaking down and crossing the BBB, and impacts the brain parenchyma in specific neuro-anatomic locations consistent with AD development. Those same toxic proteins are delivered throughout the body from their source, spreading systemic inflammation up to and including end organ disease. KB has the only Precision Biologic on the planet that’s been shown to eliminate them at their source and is developing the only diagnostic that identifies it in blood.
KB is advancing a clinically validated bio-therapeutic treatment (KB-001 Mab) for the elimination of Porphyromonas gingivalis and all of it’s virulence factors including the outer membrane vesicles and their toxic protein complex.
Keystone Bio is Backed by Scientists and Medical Professionals with over 35 Years of Experience.
Keystone Bio’s CEO and co-founder Daniel Sindelar, DMD, has played the key role globally in establishing oral pathogens causality of systemic disease including Alzheimer’s for the last 10 years. Dr. Sindelar is the first dental professional to receive a Preceptorship for Heart Attack and Stroke Prevention, is the founder and director of Oral Genomics, LLC, and Editor-in-Chief of the OSH News Network.
Peter Nara is CSO of Keystone Bio and is a highly sought-after consultant in the biotechnology community with special scientific interests in novel mechanisms of virulence, pathogenesis, and host adaptation to infectious diseases and cancer, and development of innovative approaches to diagnostic tests, vaccines, and treatment. Dr. Nara has served on many scientific advisory committees and task forces, is an author on more than 125 scientific publications and reviews, and is co-founder, president, and CEO of the Board of Biological Mimetics (BMI) for almost 20 years.
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Dr. Peter L. Nara, Chief Scientific Officer
Email: nara@keystonebio.com
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