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Aethlon Medical, Inc. Message Board

  • robert.vince robert.vince Feb 28, 2013 9:37 AM Flag

    Aethlon Medical (AEMD) Note: Multiple Shots on Goal - A Therapeutic Strategy to Address Infectious Disease & Cance

    SAN DIEGO, Feb. 28, 2013 /PRNewswire/ --Aethlon Medical, Inc. (AEMD), today released the following note authored by its Chairman and CEO, Jim Joyce.

    I recently attended a healthcare related event that featured a panel discussion comprised of life science bankers and venture capitalists. While members of this panel often had differing viewpoints, they did mutually agree they were interested in emerging therapeutic candidates that provided more than one "shot on goal," meaning the possibility of a single therapy that could address more than one disease indication.

    In the case of the Aethlon Hemopurifier®, we have created a therapeutic filtration device that selectively captures a broad-spectrum of disease promoting particles from circulation without eliminating blood components required for health. However, instead of immobilizing an antibody or agent that specifically binds to a single pathogen, we made the bold decision to deploy the capabilities of a lectin affinity agent that binds to a unique structure evolved and shared by viruses and cancer as a survival mechanism that allows disease progression to continue below the surveillance of the immune system. In the treatment of Hepatitis C virus (HCV), we have demonstrated that our Hemopurifier® can eliminate the presence of HCV in as little a seven days when utilized in combination with interferon-based therapy. Short-term administration of the same device has reduced viral load by greater than 90% in an HIV-AIDS dialysis patient who was not receiving any form of antiviral drug therapy. Additionally, government and non-government research organizations have demonstrated the Hemopurifier® captures a wide range of bioterror and pandemic threats. In regards to cancer, the same Hemopurifier® deployed in infectious disease studies has emerged to be the first therapeutic strategy to address tumor-secreted exosomes. Tumor-secreted exosomes are a vital therapeutic target as they have recently been discovered to be immunosuppressive and play significant role in seeding the creation and spread of cancer metastasis.

    So, how is it possible that one therapy can address a breadth of disease conditions? Dr. Annette Marleau, our Director of Tumor Immunology provides the following summary review for interested parties, including medical and non-medical industry shareholders of Aethlon Medical:

    Intriguingly, there are converging biological mechanisms underlying viral infections and cancer, despite the fact that these are distinct categories of disease that are typically addressed with different therapies. Common disease processes in infections and cancer include the modalities by which disease is spread and the involvement of the immune system. The latter point stems from the fact that both tumor cells and infectious pathogens are viewed as "foreign invaders" by the immune system. In response, diseased cells have evolved tactics for manipulating the immune system to their advantage in order to propagate disease. One of the key pathogenic maneuvers employed by viruses and tumors is the systemic distribution of disease-mediating particles that spread molecular information from diseased cells to healthy cells.

    Of relevance to our Hemopurifier® is the observation that critical disease-mediating particles in many viral infections and cancer display high-mannose glycoproteins on their surfaces. These surface features arise during the process of glycosylation, whereby carbohydrate residues such as mannose are tagged onto proteins to ensure proper protein assembly and function in healthy cells. Not surprisingly, this process becomes perturbed in several disease conditions, thereby changing the biologic functions of proteins. To define the glycoprotein signatures associated with specific disease conditions, researchers have applied panels of carbohydrate-binding proteins (lectins) to determine the relative compositions of specific carbohydrate residues in cellular material. Extrapolating on the use lectins as research reagents for biomarker discovery, our device platform leverages the specificity of lectins for glycoprotein-coated particles for therapeutic affinity capture.

    Among the spectrum of targets of the Hemopurifier® are enveloped viruses, a broad group of infectious pathogens that are enriched for high-mannose glycoproteins on their outer surfaces. The envelope glycoproteins have well-recognized roles in viral attachment and integration into host cells (1). Scientific studies have demonstrated that lectins have potent anti-viral activity by virtue of their interference with the functions of envelope glycoproteins. Indeed, the current version of the Hemopurifier® has been demonstrated to capture a spectrum of enveloped viruses including HIV, Dengue virus, orthopoxviruses (vaccinia and monkeypox), influenza viruses (H5N1 bird flu, 1918 Spanish flu), and Ebola.

    In addition to addressing viral infections, the Hemopurifier also captures cancer-derived exosomes that also display high-mannose glycoproteins on their outer surfaces (2). Exosomes are membranous nanovesicles secreted by diverse tumor types that act as inter-cellular messengers to spread oncogenic signals. Evidence is emerging that cancer exosomes are involved in practically every aspect of malignancy, including apoptosis of immune cells, tissue invasion, angiogenesis, metastases and resistance to therapeutic drugs. The genomic and proteomic content of exosomes, as well as the exosome load in the circulation, are known to correlate with tumor stage and metastasis, suggesting that exosomes can serve as disease biomarkers (3,4). Accordingly, exosomes have emerged as critical targets in cancer care, and there is currently an unmet need for means of targeting these nanovesicles therapeutically.

    Based on their common glycoprotein signatures, the biogenesis of virions and exosomes has been suggested to share a conserved evolutionary pathway (5). These nano-sized particles (both in the 50-300 nm range) use their heavily glycosylated surfaces for entry into target cells, where virions and exosomes transfer pathogenic information in the form of proteins and/or genetic material. These particles also hijack the intracellular machinery to affect cell growth and survival pathways, while also promoting the formation of more disease-mediating particles. Indeed, newly generated virions and exosomes are both secreted by budding off from the plasma membrane of diseased cells, during which time it is believed they inherit glycoprotein-rich membrane components (6). Thus, the fields of viral and cancer immunology converge mechanistically at the level of the glycoprotein "fingerprints" on key disease-mediating particles.

    The intersection of the pathways exploited by virions and exosomes is exemplified by the ability of certain viruses to package their infectious material into exosomes. For example, HIV-infected cells secrete exosomes containing Nef or "Negative Factor", an abundant HIV protein that induces death of CD4+ T cells, a hallmark of AIDS (7). Viruses and exosomes can therefore act as co-dependent entities for spreading infection and impeding host immunity. A validation study conducted by our collaborators at the Morehouse School of Medicine revealed that the Hemopurifier® captures NEF exosomes and therefore holds promise as an anti-viral strategy for co-targeting both Nef exosomes and HIV virions in circulation.

    Collectively, these lines of evidence provide a compelling scientific rationale for why the Hemopurifier® is a candidate broad-spectrum countermeasure against both viral pathogens and cancer. In both of these clinical scenarios, we propose to advance the Hemopurifier as an adjunct to standard of care therapies for reducing the systemic burden of disease-mediating particles and unmasking the native immune response in patients.

    (1) Balzarini J. Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy. Nat Rev Microbiol 2007;5:583.

    (2) Batista BS et al. Identification of a conserved glycan signature for microvesicles. J Proteome Res 2011;10:4624.

    (3) Taylor DD and Gercel-Taylor C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 2011;33:441.

    (4) Henderson MC and Azorsa DO. The genomic and proteomic content of cancer cell-derived exosomes. Front Oncol 2012;2:38.

    (5) Krishnamoorthy L et al. HIV-1 and microvesicles from T cells share a common glycome, arguing for a common origin. Nat Chem Biol 2009;5:244.

    (6) Wurdinger T et al. Extracellular vesicles and their convergence with viral pathways. Adv Virol 2012:767694.

    (7) Lenassi M et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 2010;11:110.

 
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