CSO Simmaron Research ; MIDD member, @RedefiningMECFS; CoFounder/Sci. Director of SIMMPHARM: Professor (adj) @UWM; Neurobio; ME/CFS; Drug design and development
Watch! Dr. Avik Roy & Dr. Gunnar Gottschalk of @RedefiningMECFS share how six years of work on the molecular mechanisms of #MECFS has led to one of the only ongoing clinical trials specifically designed around a defined biological target.
https://t.co/axR1nyC1Ev
#MEAwarenessHour
Our team @RedefiningMECFS@ggottschalkPhD continues to perform ground-breaking research in decoding the role of ATG13 in chronic inflammation and now our new research (Toriola M https://t.co/WYpvXqg8Oq.) is now published in @SpringerNature’s Q1 immunology journal Inflammation Research.
https://t.co/LHUUCTKTOj

Background: CD40 is a key surface antigen expressed on macrophages and other myeloid cells, where it plays a central role in innate immunity by sustaining their inflammatory phenotype. In our earlier study (Immunologic Res 2025) , we demonstrated that the impaired autophagy can trigger sub-threshold infiltration of CD40-immunoreactive macrophages into the vasculature of skeletal muscle tissue. This infiltration contributes to chronic inflammatory changes affecting muscle-serving nerve fibers.
Findings: In our current work, we delineate the underlying mechanism. We demonstrate that the genetic depletion of atg13 gene and the subsequent autophagy impairment may initiate a series of metabolic changes in myeloid cells. These changes start with the deficit in mitochondrial energy metabolism (confirmed by Seahorse analyses of OXPHOS and glycolysis), then the augmentation of reactive oxygen species ( Mito-ROS assay), then the nifrosylative inactivation of cellular deacetylase enzyme called SIRT1 , which maintains the acetylation status of NF-κB. These series of metabolic changes drive the induction of the inflammatory phenotype in perivascular macrophages. Along with CD40, we examined the impact of atg13-dependent autophagy impairment in the expressions of other surface antigens such as CD86, CD163, and CD206 in the context of inflammatory response in myeloid cells.
Summary: The pathway we describe highlights how NF-kB-mediated inflammatory changes in myeloid cells may contribute to the neurogenic symptoms of muscle fatigue, post-exertional malaise, and potentially post-infectious fatigue syndromes.
@MECFSNews@UWM
Excited to contribute a research with @RedefiningMECFS, @ggottschalkPhD on ATG13's role in chronic fatigue, recently accepted by Inflammation Research of @SpringerNature.. The full paper is under production now. Our research is timely and relevant as another study in Nature Communications (Hu et al. PMID: 41309545) linked ATG13-binding protein FIP200 in long COVID genetics. @MECFSResearch@PlzSolveCFS@MEResearchUK@UWM
Simmaron @RedefiningMECFS@ggottschalkPhD is excited for the early preclinical results of our small molecule-inhibitors SIMMPYRA-1 and 2 to modulate STAT signaling events in reducing chronic inflammation associated with mononucleosis and cytokine upregulations.@BCRFcure@PlzSolveCFS
Rapamycin, a potent inhibitor of mTOR, has been studied for its role as an autophagy inducer and also in immuno rejuvination. Its been approved by FDA for its application in cardiac restenosis and cancer management. Recently, we launced a decentralized clinical trial for low dose rapamycin in the amelioration of clinical symptoms of ME/CFS. We have some exciting data on the alleviation of clinical symptoms of ME/CFS and improvement of overall autophagy. The trial data has been published in our most recent article in the Journal of Translational Medicine ( Impact factor 8.5). Congrats to Brian T Ruan , the first author, who just left Cornell University to study medicine in Tufts University. Our clinical leaders including @StephanieGrach, David Kaufman, and Lucinda Bateman. Congratulations to @ggottschalkPhD the CEO of @RedefiningMECFS and one of the PIs in this study. @PlzSolveCFS@MECFSResearch@MayoClinic@UWM
https://t.co/WRqWao1ks5
The high resolution analysis is currently being studied to understand the molecular effect of rapamycin. We are identifying fast versus slow drug metabolizers, correlation with history of viral infection, duration, symptom severity and different other factors. The customized treatment is not the most time and cost effective strategy, but may be that analysis will demonstrate the dosing regimen and the treatment window.
@AndrewG76201347 We heard similar stories from other centers. All data recorded in RedCap digital server maintained by Cornell University scientists. All data was assessed by certified statisticians.
@Pnina3434 Definitely, there may be a gender-biased response. But, the heterogeneous effect does not necessarily depend on gender only. There may be other reasons such as age , duration of the disease, severity of the disease, history, comorbidities, metabolism rate of the drug etc.
Patients with post-infectious fatigue demonstrated significant recovery from PEM symptoms. Although statistically low numbers in our pilot trial as because we have started with few cases, but we have a larger sample size in our phase-II trial and we are getting a strong response.
The #UWM community extends its heartfelt sympathies and condolences to the @MarquetteU lacrosse team and the entire Marquette community for the tragic loss of its two student-athletes. We are keeping you in our thoughts.