Low-dose Rapamycin in ME/CFS and PCS

In his presentation, Dr. C. Gunnar Gottschalk reported on follow-up results from a decentralised clinical trial investigating low-dose rapamycin (sirolimus) in ME/CFS. He focused on a subgroup of patients with overactive mTOR signalling — a cellular process that, when dysregulated, can impair autophagy, the cell's own protein clean-up system. Preclinical work in animal models showed that mTOR overactivation or direct suppression of the autophagy pathway can produce PEM-like behaviour, immune cell infiltration with M1 macrophage polarisation, and abnormal peripheral nerve signalling — supporting the rationale for this target. In a Phase 1 pilot, patients received rapamycin in a gradual dose increase over about 90 days, each serving as their own control. Safety and feasibility were good; mild, temporary gastrointestinal side effects occurred during dose escalation in a small number of participants, and serum biomarkers of autophagy changed in the expected direction. Phase 2 introduced a standardised compounded formulation of sirolimus, sex-specific dosing, centralised laboratory testing, enhanced biobanking, and a longer observation period of about 120 days. Of the participants who started treatment, the majority completed the main study period; about a third were classified as responders, with improvements across multiple questionnaires covering physical function, fatigue, sleep, and cognitive performance. Laboratory analyses in a subset of responders showed increased energy production capacity in immune cells, which correlated with symptom improvement. Gottschalk emphasised that the study is open-label and without a placebo arm, and concluded that rapamycin is promising and well tolerated, but that a placebo-controlled randomised trial and better criteria for patient selection are still needed.