Ampligen and hypometabolism

Background

A few days ago Naviaux and colleagues have provided convincing proofs for the presence of an hypometabolic state in chronic fatigue syndrome (CFS) patients, with a pattern opposite to the one seen in response to acute infections. Naviaux et al. express the hypothesis that the metabolic shut down described in their paper “may represent a fundamental response to oppose the spread of persistent viral and intracellular bacterial infections” (Naviaux RK et al., 2016).

CFS is a condition without a definitive cure, although some pharmacological interventions have shown some efficacy in subgroups of patients. One of them is rintatolimod (brand name: Ampligen), a viral double stranded RNA (dsRNA) which selectively binds to toll like receptor 3 (TLR3), thus contributing to the induction of antiviral defenses (Gowen, BB et al., 2007). Approximately 30-40% of CFS/ME patients can be expected to respond beneficially to rintatolimod, according to the results of several clinical trials (Mitchell WM, 2016).

Ampligen

The first hypothesis for the efficacy of Ampligen in a subgroup of CFS patients (perhaps the most obvious one) is that it may help fighting some ongoing viral infection. If a virus was the permanent threat which mantains the hypometabolism described by Naviaux and collegues, then removing that threat could help ending the dauer-like hypometabolism. As only a subgroup of CFS patients might have the hypometabolism sustained by an active viral infection, this may be the reason why Ampligen works only for some of them.

But another feasible explanation for the efficacy of Ampligen in a subset of CFS patients, might be the following one: the positive effect could not be linked to its anti-viral activity, but could be due to its ability to artificially induce the immune response of an acute viral infection. As the hypometabolism described by Naviaux et al. has not evolved to manage an acute infection, our organism might decide to turn it off in order to shift towards the acute infection mode. At this point it might be easier for the metabolism to turn back to a normal level, instead of the previous hypometabolic state.

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