There is an enormous amount of treatment discussion happening across the ME/CFS, Long COVID and related complex chronic illness communities. Some insights have meaningful evidence behind them. Others are much earlier and still largely hypothesis-driven. Here are eight treatment signals that surfaced this week, along with what the evidence currently tells us: Methyldopa: A new retrospective series of five patients with hyperadrenergic POTS reported improvements in orthostatic symptoms and sleep. It’s a very small study, but an interesting signal around central sympathetic modulation that may be worth watching. Bezisterim (NE3107): The Phase 2 ADDRESS-LC trial did not reach statistical significance on any of its 22 individual endpoints in the overall population, although 21 of 22 numerically favored treatment. Exploratory subgroup signals emerged, but we need the full peer-reviewed results to better understand effect sizes, subgroup definitions and safety. Watching carefully. Injectable NAD+ / oxaloacetate: These are often discussed together as metabolic approaches, but the evidence is quite different. Injectable NAD+ currently lacks controlled clinical-outcomes evidence, including established efficacy data in ME/CFS. Oxaloacetate, by contrast, has been tested in an 82-person randomized, double-blind controlled ME/CFS trial at 2,000 mg/day, where it significantly reduced fatigue compared with control. The study was relatively small and had an important commercial conflict of interest, so replication would be important to strengthen the finding. CSF leak evaluation: This may be more important as a diagnostic signal than a treatment signal. In a study of 34 patients with imaging-confirmed spontaneous intracranial hypotension (SIH), 35% met POTS criteria. Blood patching and surgery are treatments for confirmed SIH, making appropriate diagnostic evaluation important before intervention. This is one of our focus areas for CODA CCD. Enterosgel: A double-blind randomized trial in 440 people with IBS-D found a higher responder rate with Enterosgel than placebo, 37.4% vs. 24.3%. Important caveat: this is evidence in diarrhea-predominant IBS, and shouldn’t be extrapolated to constipation-predominant disease or gastroparesis. Bispecific T-cell engagers: Very early autoimmune data are emerging. In a Phase 1 SLE study, 12 people were treated, with encouraging disease-activity signals among the 10 evaluable participants. But there are currently no ME/CFS data and no validated ME/CFS biomarker for selecting patients for this approach. We should be digging further. @CODA_research