{"id":12006,"date":"2017-03-27T07:04:05","date_gmt":"2017-03-27T07:04:05","guid":{"rendered":"http:\/\/wames.org.uk\/cms-english\/?p=12006"},"modified":"2017-03-27T07:04:05","modified_gmt":"2017-03-27T07:04:05","slug":"genes-mitochondria-autoimmunity-cfs-prof-alan-lights-research","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/genes-mitochondria-autoimmunity-cfs-prof-alan-lights-research\/","title":{"rendered":"Genes, mitochondria, autoimmunity & CFS: Prof Alan Light’s research"},"content":{"rendered":"

Health rising<\/strong> blog post, by Cort Johnson, 23 Feb 2017: Genes, Mitochondria, Autoimmunity and Chronic Fatigue Syndrome: The Alan Light Talk<\/a><\/p>\n

Dr. Light has said that he wants to do for fatigue what researchers have done for pain; that is uncover the molecular pathways that cause fatigue.\u00a0 Some time ago Light presented one of the most spectacular graphs of ME\/CFS ever done. I still remember the gasp that filtered through the IACFS\/ME conference when Dr. Light showed the slide below . It showed the levels of molecular receptors associated with fatigue and pain skyrocketing after exercise in white blood cells.<\/p>\n

\"\"<\/p>\n

The most famous graph in ME\/CFS history<\/strong>
\nThe healthy controls are on top and the ME\/CFS patients are below. It was even worse than it seemed. In a 2011 Bateman Horne Center video, Dr. Light explained that the differences were so extreme that he had to transform the data into log scale format in order to fit the graph on the page.\u00a0 The expression of some genes was 10 times greater in the ME\/CFS patients as in the healthy controls.<\/p>\n

Even 48 hours later \u2013 still well within the post-exertional malaise (PEM) period for many with ME\/CFS\/FM \u2013 the gene expression was still incredibly high relative to the controls.<\/p>\n

Light has found, by the way, that many people with ME\/CFS (70%) fit the criteria for FM.\u00a0 When Light compared ME\/CFS patients with FM vs ME\/CFS without FM he found only a few differences. When he looked at FM patients without fatigue, though, they looked exactly like the healthy controls. That indicated that the Lights were really zeroing in on how fatigue is produced.<\/p>\n

A key distinction between FM patients without fatigue and ME\/CFS and FM patients with fatigue emerged when the Lights looked at the baseline findings. It turned out that ME\/CFS patients looked like healthy controls at baseline but the \u201cpure\u201d FM patients without fatigue looked very different.\u00a0 The expression of three genes were dramatically elevated \u2013 so dramatically, in fact, that Light suggested that they might not be able to get any higher during exercise.<\/p>\n

The fact that the rest of the genes were unaffected by exercise could explain why studies suggest that exercise seems to work so much better in FM than in ME\/CFS. FM patients with ME\/CFS characteristics do get knocked out by exercise, but the \u201cpure\u201d FM patients \u2013 which make up a considerable portion of the FM population \u2013 don\u2019t.<\/p>\n

Light did, however, find a startlingly different subgroup hidden within the ME\/CFS population. After putting them on the bike this rather large group (40% of the study) looked exactly like the healthy controls with the exception of one gene called the alpha 2A receptor (AD2A).<\/p>\n

This ubiquitous receptor causes the blood vessels to constrict in order to keep blood from pooling in our legs when we stand. The expression of that gene plummeted in the ME\/CFS subgroup. That suggested that when those ME\/CFS patients most needed their blood vessels to constrict in order to pound more blood into their muscles, the gene that did that pooped out. Not surprisingly, 70% of the people with this gene expression signature have orthostatic intolerance.<\/p>\n

(Talk about from bench to bedside or vice versa. Dr. Light found this group when Dr. Bateman told him about a young man she could not figure out at all. Looking at the gene expression data, Light found zero increase in his ADR2A gene expression. Light then went back and specifically looked at this gene and found this major group characterized by orthostatic intolerance (OI). Unfortunately most OI drugs do not work on these patients; midodrine works for a short period but has side effects.\u00a0 What a nice example of a physician and researcher working together to break new ground.)<\/p>\n

It\u2019s important to note that the Lights were not looking at the cause of chronic fatigue syndrome (ME\/CFS) \u2013 they were looking at the effects of the cause. Something, they believed \u2013 probably in the immune system \u2013 was causing the gene expression of their immune cells to go bonkers during exercise.\u00a0 It could be a virus, it could be an autoimmune process, it could be toxins, it could be any number of things.<\/p>\n

The search for the cause came next\u2026. read more<\/a><\/p>\n

The Gist<\/strong><\/p>\n