{"id":11969,"date":"2017-02-24T08:48:41","date_gmt":"2017-02-24T08:48:41","guid":{"rendered":"http:\/\/wames.org.uk\/cms-english\/?p=11969"},"modified":"2017-02-24T08:48:41","modified_gmt":"2017-02-24T08:48:41","slug":"citric-acid-cycle-is-deficient-in-people-with-mecfs","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/citric-acid-cycle-is-deficient-in-people-with-mecfs\/","title":{"rendered":"Citric Acid Cycle is deficient in people with ME\/CFS"},"content":{"rendered":"

MEAction<\/strong> blog post, by Adrianne Tillman, 22 Feb 2017: Stanford team announces breakthrough in ME\/CFS research<\/a><\/p>\n

A research team at Stanford announced yesterday that it has made some breakthroughs in understanding the metabolic cycles<\/a> that are not working properly in people with ME\/CFS that might be at the heart of the disease.<\/p>\n

Ronald W. Davis, PhD, made the announcement via YouTube. Davis directs the CFS Research Center team <\/a>at the Stanford Genome Technology Center<\/a> (SGTC).<\/p>\n

\"\"You tube video<\/strong>: Problems with metabolic cycles <\/a>(18 mins)<\/p>\n

The team\u2019s metabolomics tests on severely-ill patients\u00a0revealed problems with the citric acid cycle<\/a>. Participants\u2019 blood work showed that some of the chemicals involved in the citric acid cycle are very low, making it difficult for the patient to generate the chemicals we use for energy. Several chemicals were found to be two standard deviations away from those of healthy controls, which is serious, according to Davis.<\/p>\n

Recent research by Fluge and Mella<\/a> has also suggested that pyruvate dehydrogenase, the enzyme that helps glycolysis transition into the citric acid cycle, may be blocked.<\/p>\n

\u201cWe have not investigated that, but it is consistent with glycolysis being shut down,\u201d Davis said. \u201cWe also think that pyruvate kinase might be shut down. Those are not inconsistent and it is possible there are blocks in both of them.\u201d<\/p>\n

The problem with NIH<\/strong>
\nDavis and his team applied for federal funding from the National Institute of Health<\/a> (NIH) for the research that led to the data showing the dysfunctional citric acid cycle in people with ME\/CFS. The NIH turned down both of his grants \u201cbecause we were trying to do discovery, and they wanted us to only do hypothesis testing,\u201d Davis said.<\/p>\n

\u201cI said to them: the scientific method is first observation, then hypothesis. And if you have virtually no observations you can\u2019t generate a good hypothesis. I think one of the big problems we have is that we do not know enough at the molecular level to generate hypotheses.\u201d<\/p>\n

Technology to screen drugs without using patients<\/strong>
\nDavis also announced a device that the Stanford team has developed to test metabolic functions, which will enable them to do mass screenings of drugs without the time and cost restraints of using patients.<\/p>\n

The device is about the size of a computer chip. It has a small channel in it to accommodate a tenth-of-a-drop of blood, all that is needed for this assay.\u00a0It has 2500 electrodes in it, and each electrode is sampled 200 times a second. This generates a massive amount of data.<\/p>\n

Davis explains how the device works:<\/p>\n

\u201cWhat we have noticed from this device is that if we put bacterial population into this, we will get a certain electrical impedance signal. If we then add an antibiotic that kills the bacteria, the electrical impedance will rapidly increase. If the bacteria are resistant to the antibiotic, we see no change.<\/p>\n

\u201cSo, if we put healthy cells and their serum into the device, it is pretty stable and does not change. If we put in ME\/CFS cells and their serum, it doesn\u2019t change. However, if we put a demand on the cells, we require them to consume energy, and that demand is seen in this graph where there is a slight dip in the healthy controls \u2013 but they handle that demand quite well and don\u2019t change after that \u2013 however the cells from the ME\/CFS patient shows a rapid increase in impedance. And that has been shown for every patient we have looked at, and also every healthy control is the same.\u201d<\/p>\n

Most importantly, the device provides a way for Davis and his team to test drugs on ME\/CFS cells and serum to see the effect.<\/p>\n

Davis noted that the rapid rise in impedance is caused by the serum, not the cell, which means that there is something being released into the serum that may be causing or contributing to symptoms.<\/p>\n

\u201cIf it is in the serum, we probably can find it,\u201d Davis said. \u201cAnd that is what we\u2019re trying to do now, which is find the component or components \u2013 most likely plural \u2013 that is causing this effect\u2026 Now this a good hypothesis, and we are now testing it.\u201d<\/p>\n

Davis said that the next step is to use the device to test the effects of various drugs on the cells and serum of ME\/CFS patients. For example, Davis\u2019 team found that adding ATP to unhealthy ME\/CFS cells and serum made the cells respond normally. The team also plans to test drugs that many ME\/CFS patients have reported helpful using this device, such as Valcyte and Rituximab.<\/p>\n

If the device turns out to be a good diagnostic test for ME\/CFS, Davis said his team will disseminate information to doctors\u2019 offices.<\/p>\n

This device may be applicable to other diseases as well, including Lyme and Fibromyalgia.<\/p>\n

The\u00a0magnetic levitation device<\/strong>
\nDavis and his team have also developed a magnetic levitation\u00a0device which\u00a0separates cells based on their magnetic properties. The device is small and can fit onto an iPhone.\u00a0 This device can be used to separate and examine cells with differing properties, which has broad applications, including examining specific cell types in ME\/CFS patients.\u00a0 The magnetic levitation device costs 5 cents per assay.<\/p>\n

\u201cWe\u2019re accumulating a list of things that we are trying with this device,\u201d Davis said.<\/p>\n

\u201cOne of our focuses is on developing engineered biosensors and devices. We also have a synthetic biology core that is used to develop new ways to do production of drugs and test drugs\u2026\u00a0So we have a heavy focus on how to reduce cost of tests and simplicity of those tests and portability,\u201d Davis said.<\/p>\n

The Open Medicine Foundation (OMF) is helping fund the work of Dr. Davis\u2019 CFS Research Center team at SGTC. So far, their breakthroughs have been achieved by doing one experiment at a time, week-by-week. At this point, the team is ready to ramp up the project in order to carry out multiple parallel investigations to get answers as fast as possible. However, substantially more funding is needed for this to happen.<\/p>\n

Opportunity to donate to Stanford’s research<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

MEAction blog post, by Adrianne Tillman, 22 Feb 2017: Stanford team announces breakthrough in ME\/CFS research A research team at Stanford announced yesterday that it has made some breakthroughs in understanding the metabolic cycles that are not working properly in … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[2781,3526,2166,3525,1920,1924],"class_list":["post-11969","post","type-post","status-publish","format-standard","hentry","category-news","tag-citric-acid-cycle","tag-magnetic-levitation-device","tag-me-action","tag-metabolic-cycles","tag-prof-ronald-w-davis","tag-stanford-university"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-373","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/11969","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=11969"}],"version-history":[{"count":2,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/11969\/revisions"}],"predecessor-version":[{"id":11980,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/11969\/revisions\/11980"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=11969"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=11969"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=11969"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}