Keystone Bio Advances a Fuller Explanation of the Toxic Virulence Factors of Porphyromonas Gingivalis as a Primary Driver of Sporadic Alzheimer’s Disease and Chronic Inflammation


ST. LOUIS – (COMMERCIAL THREAD) – Keystone Bio, a biotechnology company, is a pioneer in the development of precision biologics to eliminate Porphyromonas gingivalis (Pg), and publishes groundbreaking data which shows that toxic bacterial proteins of Pg in the mouth are released in the blood and crosses the Blood-Brain Barrier (BBB) ​​as a primary driver of sporadic Alzheimer’s disease and chronic inflammation. These new data support a “peripheral” model of toxic blood-borne proteins of P. gingivalis delivered to the blood and brain compared to previous literature in which studies in human and animal models support the “local” brain model. of Alzheimer’s disease of gingipains. What this means for Alzheimer’s disease patients and those at early risk is that KB is developing a specific diagnosis and treatment to eliminate Porphyromonas gingivalis and the flow of these toxic proteins to the brain.

These data can now be incorporated into a more unifying “concept” and “infection hypothesis” explanation for Alzheimer’s disease (AD) and other dementia-related diseases. An increased HagA Domain virulence factor is found in many matched and aged control brain tissues. Its complex role in local and systemic inflammatory diseases is well understood and further demonstrates the systemic delivery through the bloodstream of the bacterial source of “gingipains” into the brain.

This groundbreaking data was featured in three posters this week at the Alzheimer’s Association 2021 International Conference.

  • Porphyromonas gingivalis outer membrane vesicles as a primary driver and source of toxic aggression and iron accumulation / deposition in Alzheimer’s disease. In this presentation, Keystone Bio presents a hypothetical model of Porphyromonas gingivalis (Pg) and discusses whether 1. either translocation to the brain from the oral cavity via blood lymphatic vessels, intracellular or via neuronal axoplasmic flow and establishing productive infection of the brain. brain leading to local production and accumulation of exo- / endo-toxins Pg (eg gingipains / LPS etc.) worms; or 2. oral peripheral infection / colonization in the oral cavity excreting exo- / endotoxins and other virulence factors in soluble form or associated with complex outer membrane vesicles (OMV) actively secreted into the blood and / or lymphatic vessels and transmigrating neurovascular endothelium with entry into the neural parenchyma and its association with iron are important and notable differences both in the pathogenesis of the disease and in the direction of treatment.
  • Continuation of the preclinical development of a clinically effective bio-therapy against Porphyromonas gingivalis. In this presentation, Keystone Bio presents the ever-growing list of vast adverse medical conditions associated with Porphyromonas gingivalis (Pg) infection associated with long-term oral colonization associated with biofilm in humans leading to a state of systemic inflammation. chronic with several organ systems. (atherosclerosis, cardiovascular, stroke, type 2 diabetes / metabolic syndrome, cancer, Alzheimer’s, etc.), in stark contrast to a cruel set of effective prophylactic treatments and / or interventions. Using multiple technologies in microbiology, protein chemistry, proteomics, molecular biology, nucleic acid and protein sequencing, immunochemistry, scanning electron microscopy, biologic development, medium and large scale hybridoma monoclonal antibody production and development and enzymology of human chimeric antibodies, an updated status of newly developed precision biology will be presented.
  • A study on the distribution of the repeated epitope of Porphyromonas gingivalis in hemagglutinin / adhesion and antigen of the gingipains HagA domain and DNA in Alzheimer’s brains. In this presentation, Keystone Bio focuses on specific bacterial infections and factors specially caused by the oral pathogen Keystone-Porphyromonas gingivalis (Pg) in humans and animal models have been shown to chronically initiate and stimulate blood systems. innate host systemic defense and inflammasomes. Over time, these compromise the integrity of the blood-brain barrier, localize in brain parenchyma neurons and supporting cells and through multiple inflammatory pathways and lead to the activation of microglia and astrocytes. . A new anti-pg bacterial monoclonal antibody currently in pre- and clinical development was used for all of the work described. Forty-six brain tissue samples (frontal and temporal biopsies) from 23 brain samples (7 AD and 16 AMC) were subjected to a liquid PCR hybridization test to detect P. gingivalis DNA. All were negative for P. gingivalis DNA. Sections of Alzheimer’s brain from several functionally distinct anatomical regions and choroid plexuses from different patients were tested by specific immunohistochemistry for Porphyromonas gingivalis antigen.

Keystone Bio further develops this groundbreaking data in our hypothesis article published in the next August issue of the Journal of Alzheimer’s Disease (prepress currently available): Porphyromonas gingivalis Outer membrane vesicles as the main driver and explanation for neuropathogenesis, cholinergic hypothesis, iron dyshomeostasis and salivary lactoferrin in Alzheimer’s disease.

Abstract

Porphyromonas gingivalis (Pg) is a primary oral pathogen in “chronic” biofilm-induced multisystem inflammatory disease (s), including Alzheimer’s disease (AD). This is possibly the only second unique identified example of a biological extremophile in the human body. A better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction is central to its diagnosis, treatment and eventual prevention. The published literature on the role of Pg in AD highlights the direct role of the bacteria in the brain in causing disease. The available evidence, although somewhat adopted, does not fully support this process as the main one. There are other pathogenic / virulence features associated with Pg which 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 between the relatively small amounts of “Pg bacteria” residing in the brain versus the rather flowery amounts and the wide distribution of one or more of its major bacterial protein toxins. In this context, the “gingipain hypothesis”, AD-related iron dyshomeostasis and early reduction of salivary lactoferrin, as well as the resurrection of the cholinergic hypothesis can now be integrated into a working model. The present article suggests that the highly evolved and developed type IX secretory cargo system of Pg producing outer membrane vesicles might better explain the observed diseases. It is therefore hoped that this article can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment and possible prevention.

Link to prepress paper>

Keystone Bio changes the course of the disease thanks to this revolutionary science.

Keystone Bio is a clinical-stage biopharmaceutical company providing novel precision disease-modifying antibacterial biotherapies to target an important and largely untreated bacterial factor of systemic inflammation that significantly contributes to multiple inflammatory diseases such as heart disease and dementia / Alzheimer’s disease. disease as well as companion diagnostics to diagnose / identify those at risk and monitor treatment.

Using KB’s proprietary methods, KB identified a toxic bacterial protein that is the primary driver of systemic inflammation. This poisonous bacterial protein complex is actively secreted in large amounts by the bacteria for its own survival, but still exhibits off-site systemic pathology in various end organs such as the brain in brain tissue for AD. This virulent protein complex is packaged in distinct outer membrane vesicles, breaking down and crossing the BBB, and impacts the brain parenchyma in specific neuroanatomical locations consistent with the development of AD. These same toxic proteins are delivered throughout the body from their source, spreading systemic inflammation to and including target organ disease. KB has the only precision biologic on the planet that has been shown to eliminate them at the source and is developing the only diagnosis that identifies it in the blood.

KB offers a clinically validated biotherapeutic treatment (KB-001 Mab) for the elimination of Porphyromonas gingivalis and all of its virulence factors, including outer membrane vesicles and their toxic protein complex.

Keystone Bio is backed by scientists and healthcare professionals with over 35 years of experience.

Keystone Bio CEO and Co-Founder Daniel Sindelar, DMD, has played a key role globally in establishing the causation of oral pathogens in systemic diseases, including Alzheimer’s disease, in over the past 10 years. Dr. Sindelar is the first dental professional to receive a preceptorship for the prevention of heart attacks and strokes. He is the founder and director of Oral Genomics, LLC and editor of the OSH News Network.

Peter Nara is CSO of Keystone Bio and is a much sought-after consultant to the biotechnology community with particular scientific interests in novel mechanisms of virulence, pathogenesis and host adaptation to infectious diseases and cancer, and the development of innovative approaches for diagnostic tests, vaccines, and treatment. Dr Nara has served on numerous scientific advisory committees and working groups, is the author of over 125 scientific publications and journals, and is co-founder, Chairman and CEO of the Board of Biological Mimetics (BMI) for nearly 20 years.

Forward-looking statements

This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements relating to future financial and / or operating results, future growth of research, technology, clinical development and potential opportunities for Keystone Bio and Services, as well as other statements regarding future expectations, beliefs, objectives, plans or prospects expressed by management constitute forward-looking statements.

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