The Convergence of Infectious Diseases and Noncommunicable Diseases Proceedings of a Workshop (2019) / Chapter Skim
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3 Emerging Research on Associations Between Infectious and Noncommunicable Diseases
3 Emerging Research on Associations Between Infectious and Noncommunicable Diseases
Pages 23-38
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From page 23... ...
The presenters identified knowledge gaps and discussed overall implications for further research and practice. They also described cutting-edge study designs and tools being used to explore emerging associations between infectious diseases and NCDs, as well as the methods used to identify causal links and their temporal relationships.
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Neurobiology of Alzheimer's Disease Lynch explained that over the past 30 years, drug development for Alzheimer's disease has focused primarily on the beta amyloid plaques in the brain of patients, a strategy that has not produced effective treatments (Soscia et al., 2010; Kolata, 2016; Kumar et al., 2016; Gosztyla et al., 2018)
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P gingivalis is a common infection in the mouth -- half of elderly people have symptomatic periodontal disease and 80 to 90 percent are infected with this bacterium, Lynch reported.
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gingivalis, inducing Alzheimer's pathology after 22 weeks (see Figure 3-1) .3 After entering the brain, the bacteria caused chronic, lowgrade inflammation, which triggered beta amyloid plaques, caused activated microglia, and induced Tau tangle-like neurons.
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From page 27... ...
In addition to addressing causation, the mouse model may also provide a new model for drug development that will be more translatable to human studies. Initial Clinical Studies on Gingipain Inhibition Based on these breakthroughs, Lynch's company is developing a new drug, COR388, to treat patients with mild to moderate Alzheimer's disease.
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EPSTEIN-BARR VIRUS IN AUTOIMMUNE AND INFLAMMATORY DISEASES John Harley, founding director of the Center for Autoimmune Genomics and Etiology at Cincinnati Children's Hospital Medical Center, provided a genomic perspective on EBV in autoimmune and inflammatory diseases. EBV infects more than 95 percent of the adult human population (Cohen, 2000)
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For instance, lupus, an idiopathic inflammatory disease affects an estimated 200,000 people in the United States and millions of people worldwide (Rees et al., 2017) .6 The molecular mimicry process that causes lupus may originate from humoral responses to EBV nuclear antigen 1 (Harley and James, 2006)
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to determine the loci where the transcription factor shares a variant with the disease. Looking at 1,544 human datasets, they found that the co-factor for transcription EBV nuclear antigen 2 (EBNA-2)
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Effect of Modern Lifestyle Factors on the Microbiota Nagler presented the hypothesis that modern industrialized lifestyle factors trigger shifts in the composition of our commensal8 microbiota in ways 8 Commensalism refers to the association between two organisms in which one benefits and the other is neither harmed nor benefits.
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She proposed that in a setting of genetic susceptibility, these lifestyle factors are driving up the prevalence of food allergies. Colonizing Healthy Microbiota to Protect Against Allergic Response To address the increasing prevalence of food allergies, Nagler and her colleagues have collaborated with a group at the University of Naples that provided fecal samples from 20 healthy infants and 20 infants with cow's milk allergy (CMA)
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The results from 100 gnotobiotic mice demonstrate that the mice colonized with the healthy infant microbiota were protected from an allergic response to food. The mice that received microbiota from CMA donors were susceptible to anaphylaxis, as were the germ-free mice to a lesser extent.
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To this end, ClostraBio is developing polymers that have conjugated microbial metabolites. The first candidate is butyrate; however, they are also considering live biotherapeutic approaches and prebiotic dietary fibers to present bacteria with their substrate and all of the components they need to be able to optimally produce the metabolites.
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Jay Varma, senior advisor at the Africa Centres for Disease Control and Prevention, asked if there are any epidemiologic associations between populations with different levels of dental hygiene and the occurrence of Alzheimer's disease or if it is so persistently difficult to eradicate that it may not even correlate to dental caries or other issues. Lynch responded that such an analysis is not very feasible, given the large number of variable factors related to having periodontal disease and Alzheimer's.
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Harley asked Lynch if their drug has been tested for periodontal disease. Lynch replied that it has been tested in a mouse model and a naturally occurring dog model that found efficacy in periodontal disease.
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People who get a serious EBV infection during their teenage years have an increased risk of between two- and seven-fold of multiple sclerosis (Endriz et al., 2017)
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