Just a quick update on the bedbound elderly. She has mycobacterium avium-intracelulaire (aka MAC, a very common chronic bacterial infection in the frail elderly population), and her O2 saturation is normally 82%. After each dose of rapamycin, oxygen saturation would increase to 90% for a few days, and then afterward, it will dip down to 82% again. We are increasing the dose from 0.5 mg once a week to 0.5 mg twice a week.
A review of the literature showed that mTOR has a role in mycobacterium defense.
In this paper," In the face of the increasing prevalence, high mortality, and treatment challenges associated with MAC infections, new therapeutic options are urgently needed. A promising avenue of research is that of host-directed therapies (HDTs). HDTs are adjuncts to antimicrobial therapy, differing from the latter in that they target host processes rather than the pathogen itself. The goal of HDTs is to boost protective immune responses, especially those inhibited or otherwise modified by the pathogen, and prevent excessive pathological inflammation… Rapamycin and other analogs directly inhibit mTOR activity, and vitamin D blocks upstream signaling to activate mTOR During Mycobacterium tuberculosis (Mtb) infection, the activation of both intracellular or extracellular surface pattern recognition receptors (PRRs) by certain unique Mtb-associated molecules, such as lipomannan, lipoarbinomannan, phthiocerol dimycocerosate (PDIM), lipoproteins, mycolic acid and Mtb DNA/RNA, induces autophagy . Given that autophagy plays an important role in mycobacterial clearance, and MAC can survive intracellularly by blocking phagosome-lysosome fusion, enhancing autophagy through inhibition of the mTOR pathway appears to be an attractive HDT strategy)."
Echoing this, another paper noted: Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection - PubMed “In this study, we used C3HeB/FeJ mice as an experimental model to investigate the potential role of rapamycin, a mammalian target of rapamycin inhibitor, as an adjunctive therapy candidate during the treatment of Mycobacterium tuberculosis infection with moxifloxacin. We report that administration of rapamycin with or without moxifloxacin reduced infection-induced lung inflammation, and the number and size of caseating necrotic granulomas. Results from this study strengthen the potential use of rapamycin and its analogs as adjunct TB therapy, and importantly underscore the utility of the C3HeB/FeJ mouse model as a preclinical tool for evaluating host-directed therapy candidates for the treatment of TB.”
In contrast, other investigators have expressed more caution: in thie Cell article, "Therapies targeting mTOR are being explored for a number of conditions, including aging. Genetic and pharmacological mTOR inhibition can increase lifespan in yeast, worms, flies, and mice (Papadopoli et al., 2019; Saxton and Sabatini, 2017). Pilot studies of a short course of pharmacological mTOR inhibition in older human volunteers report increased responses to influenza vaccines (suggesting decreased immune senescence) and a reduction in self-reported viral respiratory infections (Mannick et al., 2014, 2018). Similarly, in lung TB patients receiving adjunctive mTOR inhibition therapy together with appropriate antimicrobial treatment had possible, transient improvement in lung function (Wallis et al., 2021). In a mouse model of severe TB, mTOR inhibition therapy induced host-beneficial or -detrimental effects depending on the treatment regimen; mTOR inhibition therapy reduced lung immunopathology in established infections when given in conjunction with an antimicrobial drug, but exacerbated lung damage and morbidity when administered alone in the early infection (Bhatt et al., 2021). Our finding that mTOR inhibitors dramatically increase susceptibility to pathogenic mycobacteria warrants caution in their use as anti-aging or immune boosting therapies in the many areas of the world with a high burden of TB."
My naive thought is that if low-dose rapamycin can strengthen the host’s immune response and rejuvenate cells, they may have a better chance of getting rid of MAC.
Feedback welcome.
