Another of our SMCI-Directed Research Studies is being conducted in partnership with Dr. Sheila Stewart of Washington University in St. Louis in collaboration with Dr. Masashi Narita of the Narita Group at Cambridge University in England. This study explores immuno-senescence and cell-cycle analysis in the pathophysiology (or functional changes that accompany a particular syndrome or disease) of ME/CFS.
As described by Dr. Stewart, recent work has shown patients with ME/CFS to have alterations in immune cells as well as in the p38 Map Kinase (p38MPAK), a key pathway critical for proper cell function.
Whether these observations are related to the symptoms associated with, is the cause of, or simply has a correlation to ME/CFS remains to be understood.
Immuno-senescence refers to the interplay between aspects of immunity, either localized or systemic, and those of senescence cells. In other words, it refers to cells that have stopped duplicating or dividing prematurely.
Factors known to trigger premature senescence include
- Oxidative stress (stress caused by improper metabolic processing)
- Telomere dysfunction (telomeres act as a type of endcap for DNA, and their dysfunction contributes to several complex diseases like cancer)
- DNA mutations/damage (which can be caused by irradiation and many other factors)
- Oncogenic pressure (improper functioning of cancer-causing genes)
Intriguingly, p38MAPK activation is an important component in the alteration of a tissue’s extracellular matrix (ECM), the function of local immune cells, and the growth and spread of tumor cells. Given the role senescence cells play in these different disease settings, it is possible that their activation contributes to symptoms in ME/CFS patients.
Results from this study have the potential to be quite significant and may include
- Expanding the role of cellular senescence in ME/CFS and providing additional context and clarity
- Identifying specific biological signatures from well-characterized patients
- Developing mechanistic insight into comorbidities associated with ME/CFS
- Uncovering potential new biomarkers that could help with rapid and effective diagnosis
- Comprehending signaling pathway interactions involved in the disease
- Supporting existing projects and hypotheses by our research organization and others as well as generating new hypotheses
- Classifying patients based on molecular alterations
- Developing precision medicine profiles, categories, and subcategories in ME/CFS with additional patients
We expect that the initial phase of this new project will be completed in 2017, with results requiring additional mechanistic investigation to establish findings as reproducible and validated targets.
Dr. Zaher Nahle, SMCI’s chief scientific officer and vice president for research, stated, “This is an important investigation addressing an area of biology in ME/CFS that is still ill defined. And we could not be more excited about our partnership with Drs. Stewart and Narita, who are leading pioneers in this field. It is our hope that this study will reveal signatures and identifiers pointing toward biomarkers and also the molecular basis for the disease and its subgroups. The results from this study will help us to hone or validate our hypotheses. And, what’s more, we will be able to seek new partnerships and assist the work of others by publishing these results alongside our collaborators.”January 13, 2017