by 
Amanda Elam, PhD, President and CEO of Galaxy Diagnostics, recently spoke at the 2021 Intracell Research Group Conference, Before Amyloid Beta: Exploring Pre-pathology Events in Alzheimer’s Disease. Videos of all of the presentations can be found here and here. Dr. Elam’s presentation can be found 53 minutes into the second video.
In this presentation, Dr. Elam discussed what she has learned at Galaxy Diagnostics about biotechnology commercialization and how these lessons speak to advancing technologies to address the infection hypothesis in Alzheimer’s disease. New ideas about the causes of Alzheimer’s are exciting, but changes to clinical practice need science-based developments in testing and treatment. And that can be a long road.
The infection hypothesis in Alzheimer’s disease is part of a larger emerging paradigm in medicine that microbiologists call the New Germ Theory of Disease (Ewald, 2008). This paradigm is also referred to as the infectious etiology of chronic disease (IOM, 2004). Cancer researchers are leading this area of discovery, demonstrating the role of infection in the development of cancer (de Martel et al 2012). Researchers in other medical specialties are also generating evidence suggesting that stealth pathogens may play a role in chronic disease (Im et al 2020). Most often, these chronic diseases are immune-mediated disorders affecting multiple systems of the body (Christen 2019).
At Galaxy Diagnostics, we have focused on zoonotic, vector-borne infections associated with asymptomatic or mild acute disease that also have the potential to lead to serious illness and death, especially in immunocompromised patients. One example is an emerging genus of bacteria called Bartonella. Bartonella henselae is the most common species of infection, but it was only discovered in the 1990s as the key agent causing cat scratch disease and several life-threatening complications in HIV/AIDS patients.
Like the Lyme disease bacteria (Borrelia species), Bartonella species represent a very challenging genus of pathogens that elude host response and hide in cells, posing significant challenges to conventional test methods for both antibodies and DNA evidence of infection. These low-abundance pathogens require advanced detection methods to overcome the poor reliability of conventional diagnostic technologies because they:
- are slow growing
- are immune evasive
- are gram negative
- cause relapsing/remitting intravascular bacteremia
- infect and hide in a wide range of cell types in the body
- and travel through multiple organ systems.
Scientists at NC State University and Galaxy Diagnostics are developing more sensitive test methods using sample enrichment methods for Bartonella species and Borrelia species, like liquid enrichment in a specialized growth medium (BAPGM™), Nanotrap® antigen capture, and droplet digital PCR to enhance the sensitivity of direct detection. These technologies have demonstrated gains in sensitivity with data published in peer-reviewed publications.
All of these technologies are used in test offerings available at Galaxy Diagnostics, but advancing these technologies is not the end of the commercialization story. We have experienced some common roadblocks like many other biotechnology companies in our early stage of market development.
A major roadblock is that all hard-to-detect emerging infections start off as “rare diseases” until research proves otherwise. The development of more sensitive detection methods is vital to establish the clinical importance of these infections. However, translating medical discoveries into clinical practice is notoriously difficult and can take decades.
Some challenges specific to the commercialization of more sensitive detection methods for low-abundance infections include the needs and desires of three groups in the marketplace:
- patients want direct access to the best possible tests with the lowest possible cost;
- doctors often seek tests that are convenient to order, especially through the big labs, with insurance coverage guaranteed, clear clinical guidance on use and interpretation, and digital access for ordering and results, with a bias toward tests that confirm their suspected diagnosis; and
- reviewers, funders, and investors are seeking technologies with big markets, with a bias toward high-throughput systems, FDA-approved IVD kits, and rapid, point-of-care assays.
Unfortunately, testing solutions for new and/or rare infections rarely meet these criteria, which results in a gap in the medical innovation pipeline for the commercialization of diagnostics for infections like bartonellosis, borreliosis, and other immune-evasive, low-abundance infections. A caution is offered for faculty innovators investigating the role of infection in Alzheimer’s disease: conventional diagnostics have limited sensitivity for infections that may be involved in neurogenerative disease, and the path to research funding and commercialization of diagnostic solutions is an extremely challenging one.
References
de Martel, C. et al. (2012). Global burden of cancers attributable to infections in 2008: A review and synthetic analysis. Lancet Oncology, 13(6), 607-615. 10.1016/S1470/2045(12)70137-7 https://pubmed.ncbi.nlm.nih.gov/22575588/
Im, J. H. et al. (2020). Antinuclear antibodies in infectious diseases. Infectious Diseases, 52(3), 177-185. 10.1080/23744235.2019.1690676 https://pubmed.ncbi.nlm.nih.gov/31718355/
Christen, U. (2019). Pathogen infection and autoimmune disease. Clinical & Experimental Immunology, 195(1), 10-14. 10.1111/cei.13239 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300646/
Ewald, P. W. (2002). Plague time: The new germ theory of disease. Anchor Books. https://www.amazon.com/Plague-Time-Germ-Theory-Disease/dp/0385721846
Knobler, S. L., O’Connor, S., Lemon, S. M., & Najafi, M. (Eds.). (2004). The infectious etiology of chronic diseases: Defining the relationship, enhancing the research, and mitigating the effects. National Academies Press. https://www.ncbi.nlm.nih.gov/books/NBK83689/
