The standard of care for most chronic inflammatory disorders are immunosuppressive drugs or palliative therapies. However, a growing number of chronic inflammatory conditions are now tied to microbiome dysbiosis + persistent infection. Under such conditions, treatments that support or activate the human immune system could improve microbiome health by allowing patients to better target persistent pathogens. Treatments that target pathogens directly are also in development. This paradigm shift in treatment, that I have called for in several papers + articles, is already underway. Here are several 2018 papers related to the topic:
Lead author: Michal Schwartz, Weizmann Institute of Science, Israel
This is definitely one of the most important papers of 2018. It describes how supporting the immune system in patients with neurodegenrative disease could form the basis of novel therapies. The team also contends that, when it comes to these neurodegenerative conditions, “autoimmunity” and immunosuppression are failing paradigms.
Paper highlight: “For decades, it was accepted that the CNS is an “immune-privileged site”…This view ascribed the inflammation in chronic neurodegenerative disease to autoimmunity. As a consequence, attempts were made to treat such conditions with immune-suppressive drugs, all of which failed”
“In conclusion, the development of a therapy that boosts the immune system in a well-controlled way, and thereby restores and/or activates brain–immune communication, is an outcome of a general shift toward the perception of the CNS as a tissue that engages in a constant dialog with peripheral immunity. Such an approach is expected to provide novel treatment modalities in order to harness common immune repair mechanisms to combat Alzheimer’s disease and perhaps other neurodegenerative diseases.”
Lead author: Rajiv Khanna, University of Queensland, Australia
This open-label, dose escalation trial evaluated the safety and efficacy of adoptively transferred in vitro-expanded EBV-specific T cells for patients with progressive Multiple Sclerosis. Clinical improvement was seen 7 of the 10 patients, with the greatest benefit for patients that received T cells with strong EBV reactivity.
Lead author: WC Chein, Tri-Service General Hospital, National Defense Medical Center, Taiwan
This retrospective cohort study found that use of anti-herpetic medications in the treatment of Herpes Simplex Virus (HSV) infections was associated with a decreased risk of dementia. The findings could be a signal to clinicians caring for patients with HSV infections, especially since the herpesviruses are implicated in a growing number of neurological conditions.
Lead author: Katherine L. Cook, Wake Forest School of Medicine
The team found that, in primates, eating a Mediterranean diet altered composition of the breast tissue microbiome + associated microbial metabolites in the region. The findings suggest that dietary changes may influence microbiome ecosystems outside the human gut.
Lead author: Gary Siuzdak, The Scripps Research Institute
The paper is an excellent introduction to the field of functional metabolomics: the use of carefully identified metabolites to modulate diverse processes like stem cell differentiation, oligodendrocyte maturation, insulin signaling, T-cell survival and macrophage immune responses. Because metabolites used in this fashion directly modulate the biology of the host, they can be potentially be used to create new treatments for a range of conditions.
Paper highlight: “Applications of Metabolomics activity screening (MAS) could be expanded to disease modulation, biofilm initiation or suppression, drug–exposome interactions, plant biology and immunotherapy. Perhaps what is most intriguing is that rather than identifying metabolites to understand pathways, we can apply metabolites to modulate physiology, thereby turning the tables on conventional thinking.”
A perfect example of functional metabolomics at work. The team found that mitochondrial proteome one-carbon metabolism is particularly blunted in aged T cells. But providing metabolites in one-carbon metabolism to the aged T cells resulted in improved activation and survival. This could could represent a new strategy to develop immunotherapies for a range of chronic conditions.