The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.
Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) is a debilitating disorder that is accompanied by reduced cytotoxic activity in natural killer (NK) cells. NK cells are an essential innate immune cell, responsible for recognising and inducing apoptosis of tumour and virus infected cells. Calcium is an essential component in mediating this cellular function. Transient Receptor Potential Melastatin 3 (TRPM3) cation channels have an important regulatory role in mediating calcium influx to help maintain cellular homeostasis. Several single nucleotide polymorphisms have been reported in TRPM3genes from isolated peripheral blood mononuclear cells, NK and B cells in patients with CFS/ME and have been proposed to correlate with illness presentation. Moreover, a significant reduction in both TRPM3 surface expression and intracellular calcium mobilisation in NK cells has been found in CFS/ME patients compared with healthy controls. Despite the functional importance of TRPM3, little is known about the ion channel function in NK cells and the epiphenomenon of CFS/ME. The objective of the present study was to characterise the TRPM3 ion channel function in NK cells from CFS/ME patients in comparison with healthy controls using whole cell patch-clamp techniques.
NK cells were isolated from 12 age- and sex-matched healthy controls and CFS patients. Whole cell electrophysiology recording has been used to assess TRPM3 ion channel activity after modulation with pregnenolone sulfate and ononetin.
We report a significant reduction in amplitude of TRPM3 current after pregnenolone sulfate stimulation in isolated NK cells from CFS/ME patients compared with healthy controls. In addition, we found pregnenolone sulfate-evoked ionic currents through TRPM3 channels were significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients.
TRPM3 activity is impaired in CFS/ME patients suggesting changes in intracellular Ca2+ concentration, which may impact NK cellular functions. This investigation further helps to understand the intracellular-mediated roles in NK cells and confirm the potential role of TRPM3 ion channels in the aetiology and pathomechanism of CFS/ME.
By Tom Whipple, Science Editor,
August 21 2018, 12:01am, The Times
More than a hundred academics have joined ten MPs and scores of patient groups from around the world to sign an open letter calling for The Lancet to reanalyse a study into treatment for myalgic encephalomyelitis (ME).
The letter follows a debate in parliament in which one MP said that the study, which is used to set NHS guidelines, “will go down as one of the biggest medical scandals of the 21st century”. The authors of the research paper stood by their findings and said that the letter represented a campaign to discredit solid research and force the retraction of papers simply because patients disagreed with their findings.
The signatories, who include academics from Harvard, Stanford, UCL and the London School of Hygiene and Tropical Medicine, said that the 2011 Pace trial, which recommended therapy and exercise as a treatment for the condition, had “major flaws” and “unacceptable methodological lapses”.
The £5 million publicly funded trial was published in The Lancet and has informed advice on treating people with ME in the NHS and abroad, but is controversial among ME sufferers. Some claim that its advice perpetuates an idea that the disease, which causes debilitating disability, is all in the mind.
The FatiGo trial concluded that multidisciplinary rehabilitation treatment is more effective for chronic fatigue syndrome/myalgic encephalomyelitis in the long term than cognitive behaviour therapy and that multidisciplinary rehabilitation treatment is more cost-effective for fatigue and cognitive behaviour therapy for quality of life. However, FatiGo suffered from a number of serious methodological flaws. Moreover, it ignored the results of the activity metre, its only objective outcome. This jeopardizes the validity of FatiGo. Its analysis shows that there was no statistically significant difference between multidisciplinary rehabilitation treatment and cognitive behaviour therapy and neither are (cost-)effective. FatiGo’s claims of efficacy of multidisciplinary rehabilitation treatment and cognitive behaviour therapy for chronic fatigue syndrome/myalgic encephalomyelitis are misleading and not justified by their results.