"Investigating the cytotoxicity of a novel treatment for Chronic Fatigue [CFS]"

[Dolphin]

Source: Advanced Science Letters
Vol. 23, #7, pp. 6851-6857
Date: July 1, 2017
URL: http://www.ingentaconnect.com/contentone/asp/asl/2017/00000023/00000007/art00203


Investigating the cytotoxicity of a novel treatment for Chronic Fatigue
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Faza Yuspa Liosha
- Institute of Cellular Medicine, Newcastle University, United Kingdom


Abstract

Background
Fatigue perception in Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME) patients under resting state was suggested to be caused by the activity of pyruvate dehydrogenase complex (PDC) kinase. PDC kinase continuously activates PDC to converts pyruvate to lactic acid causing intracellular acidosis. As a PDC kinase inhibitor, dichloroacetate (DCA) shown to reverse the intracellular acidosis. However, DCA cytotoxicity towards patient's myoblast needs to be investigated.

Aim
To assess ME/CFS cells' viability on extracellular acidification then investigating DCA ability and cytotoxicity in related to the acidification. Lastly, to manufacture pH sensitive nanosensors that effective for ME/CFS cells.

Methods
Cell viability upon acidification and DCA treatment were assessed by using fluorescent based alamarBlue(r) (Resazurin) assay. pH sensitive nanosensors were fabricated comprising FITC with TAMRA and FAM-Oregon green with TAMRA. Nanosensors were calibrated by using cell free calibration method. The nanosensors were internalised by using Lipofectamine(r) 2000.

Results
Overall, ME/CFS cells had higher viability in low extracellular pH condition compare to nondiseased cells. Further DCA supplementation enhanced ME/CFS cells viability in acidic environment. Nanosensors fabrication and calibration succeeded, yet the internalisation process was unsuccessful. Moreover, only the nanosensors using FAM-Oregon green with TAMRA generated linear calibration curve.

Conclusions
This study showed that ME/CFS cells were more resistant toward extracellular acidification and DCA treatment succeeded to enhance their ability to survive in acidic environment, yet it should be concerned that early phase may induce toxicity. Protocol for future pH sensing nanosensors fabrication may be considered using FAM-Oregon green with TAMRA combination.

Keywords: Chronic Fatigue Syndrome; ME/CFS Cells; Myalgic Encephalomyelitis; PDC Kinase

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(c) 2017 American Scientific Publishers

 

[RogerBlack]

Wikipedia https://en.wikipedia.org/wiki/Dichloroacetic_acid says that it's already used for wart removal and skin peels, and a quick google indicates it's readily available inexpensively (though perhaps not in adequate purity).

However, it also says that nerve and liver damage have occurred in some patient trials. It's not been effective really in any trial that's been done in various conditions.

Very much not something to try at home.

 

[Sidereal]

DCA is used as a treatment in some mito disorders. I figured it was only a matter of time before someone tried it for ME/CFS given the PDH abnormalities.

Risks include nerve damage (although the dose of thiamine used in this study is too low IMO):

https://www.ncbi.nlm.nih.gov/pubmed/11410919

Nerve conduction changes in patients with mitochondrial diseases treated with dichloroacetate.
Spruijt L1, Naviaux RK, McGowan KA, Nyhan WL, Sheean G, Haas RH, Barshop BA.
Author information

Abstract
Serial measurements of nerve conduction velocities and amplitudes were performed in 27 patients with congenital lactic acidemia over 1 year of sodium dichloroacetate (DCA) administration. Patients were treated with oral thiamine (100 mg) and DCA (initial dose of 50 mg/kg) daily. Nerve conduction velocity and response amplitude were measured in the median, radial, tibial, and sural nerves at 0, 3, 6, and 12 months, and plasma DCA pharmacokinetics were measured at 3 and 12 months. Baseline electrophysiologic parameters in this population were generally below normal but as a group were within 2 standard deviations of normal means. Although symptoms of neuropathy were reported by only three patients or their families, nerve conduction declined in 12 patients with normal baseline studies, and worsening of nerve conduction occurred in the two who had abnormalities at baseline. Peripheral neuropathy appears to be a common side effect during chronic DCA treatment, even with coadministration of oral thiamine. Nerve conduction should be monitored during DCA treatment.