Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?

Abstract

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic disease the pathogenesis of which remains elusive. Pragmatic proof-of-principle of the hypothetical mechanisms causing the clinical symptoms has been delivered, but it is hard to explain why some patients do respond favourably to treatment with sodium dichloroacetate (DCA), which enhances the activity of the mitochondrial enzyme pyruvate dehydrogenase, but other patients experience no benefit from this substance.

In a prospective trial including 35 ME/CFS patients, logistic regression analysis with stepwise elimination has identified 6 pre-treatment characteristics allowing for the differentiation between responders (n = 13) and non-reponders (n = 22) with high accuracy (P < 0.0001; area under the ROC-curve = 0.92). A formula was derived generating the probability of belonging to the group of responders. This finding may assist in selecting ME/CFS patients suitable for treatment with DCA, but requires further studies as to the predictive capacity of the derived formula.

Introduction

The disease called myalgic encephalopathy or encephalomyelitis (ME) commonly is accepted to include both chronic fatigue syndrome (CFS) and fibromyalgia, though the clinical signs of these diseases may be different. Also, the severity of ME/CFS is greatly variable, with most patients experiencing primarily post-exertional fatigue and poor recovery of energy, others suffering from different aspects of brain dysfunction, or muscular and articular pain, and still others presenting signs and symptoms of deregulation of the autonomous nervous system, or any combination of these. In a previous publication we have highlighted the role of immune disorder [1], and consequent inflammatory and metabolic mechanisms in the pathogenesis of ME/CFS. We have introduced the use of sodium dichloroacetate as a possible treatment aiming at the correction of one of the putative metabolic dysfunctions by increasing the activity of the enzyme pyruvate dehydrogenase [2]. However, only approximately 35–40% of patients do benefit from this treatment by significant improvement of the health situation (“responders”), whereas the majority of patients do not (“non-responders”) [3]. The fact that it was possible to discriminate to some extend between responders and non-responders based on pre-treatment characteristics was remarkable, but needed further analysis.

In the present study we have performed a more thorough analysis of the data on a larger cohort of patients, including 13 reponders and 22 non-responders.