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Gene Expression & CFS?

Messages
5
Location
Sydney, Australia
Curios to know what work has been conducted with regards to Gene Expression or Gene therapy with CFS type illnesses?

I ask because Dr Kolgenik of OMI (I'm a patient) mentioned to me something during my last Rituxan infusion about the role of gene expression in his current research which I didn't quite grasp the logic of conducting, so wondering who out there might know a bit more about Genes/Genetic Expression, MRNA.

Have always found it peculiar why there is such a diverse range of symptoms, severity of symptoms, severity of illness, progression of illness, gender tilt, bell curve age of onset, context of onset if indeed there may be one, and more interestingly why some patients appear to be responding well to some current treatments and others not. In this respect I am referring to Rituxan & Valcyte as the big hitters for the moment.

Beyond what Dr Kogelnik is focusing on with regards to gene expression and the above 2 drugs (ostensibly) in an effort to better identify treatments that will most likely will prove beneficial (my interpretation), I can't help but wonder why a far greater focus on DNA/MRNA data profiling isn't top of many researchers agenda?

I'm going back some time now, but a lecturer of mine many years ago stated that when genetic profiling becomes a cost effective research tool (which it now is) then one would expect an explosion in the kinds of targeted gene therapy research and treatments there following. I've really no idea who is or isn't looking at CFS through this prism of research, but would be very interested to know who is. I ask the question because Rituxan has shown itself to have a marked benefit for a limited period of time for only some CFS patients, which has given some credence to the view that CFS has has a strong underlying genetic component, but to that end I would really like to know if anyone is doing any substantial genetic research in the context of CFS.

If anyone knows of anyone looking at this area of research I would be grateful if anyone could please send me URL links or contact information as I do believe this is an area of research worth investing in.

Thanks,

Ben
 

Ruthie24

Senior Member
Messages
219
Location
New Mexico, USA
I know Dr.Nancy Klimas in FL, and Dr. Bateman and the Lights (husband- wife team of docs) in Utah have done some gene expression studies particularly related to how exercise impacts their expression. For example, in a small study, Dr. Klimas showed that in CFS patients, exercise caused gene expression to change in such a way that caused autonomic dysfunction followed by immune dysfunction.

Dr. Lucinda Bateman published a study showing specific changes in gene expression which caused specific changes is cytokine expression after exercise in certain groups of CFS patients.

I just gave my paper copies to my POTS doc so I'll see if I can find the links again.
 
Messages
5
Location
Sydney, Australia
Great to hear. Keen to see who is doing what in this research space, thanks for just posting a response wasn't sure if I would hear from anyone on this front. Regards, Ben
 

ukxmrv

Senior Member
Messages
4,413
Location
London
Dr Kerr did some gene expression work in the UK. I think that there were a couple of papers. Was one of the patients used in one study but forget which one.

http://www.ncbi.nlm.nih.gov/pubmed/18462164

Abstract
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of >or=2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction. Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

http://www.ncbi.nlm.nih.gov/pubmed/19007540

Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis.
Kerr JR.
Source
St. George's University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. jkerr@sgul.ac.uk
Abstract
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. Following two microarray studies, we reported the differential expression of 88 human genes in patients with CFS; 85 of these genes were upregulated and 3 were downregulated. The top functional categories of these 88 genes were hematologic disease and function, immunologic disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from CFS/ME patients revealed seven subtypes with distinct differences in Short Form (SF)-36 scores, clinical phenotypes, and severity. Gene signatures in each subtype implicate five human genes as possible targets for specific therapy. Development of a diagnostic test for subtype status is now a priority. The possibility that these subtypes represent individual host responses to particular microbial infections is being investigated and may provide another route to specific therapies for CFS patients.
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
Curios to know what work has been conducted with regards to Gene Expression or Gene therapy with CFS type illnesses?

I ask because Dr Kolgenik of OMI (I'm a patient) mentioned to me something during my last Rituxan infusion about the role of gene expression in his current research which I didn't quite grasp the logic of conducting, so wondering who out there might know a bit more about Genes/Genetic Expression, MRNA.

Researchers are using an Interferon [gene expression] signature to predict response/nonresponse to Rituxan in rheumatoid arthritis patients--

http://www.ncbi.nlm.nih.gov/pubmed/22540992

In the Kerr gene expression study mentioned above the interferon signaling pathway topped the list of those associated with ME/CFS--

http://www.ncbi.nlm.nih.gov/pubmed/18462164

Perhaps Dr. Kogelnik is exploring these & other areas?
 

vli

Senior Member
Messages
653
Location
CA
apologies if i sound a bit dense, brand new to gene expression. my question is: have any ME treatments resulted directly from work done in gene expression? Thanks.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
my question is: have any ME treatments resulted directly from work done in gene expression? Thanks.
Not that I'm aware of. Jonathan Kerr used to speculate about immuno-modulators, as a potential treatment for ME, based on his gene expression work, but I don't think he ever got around to setting up a trial.
 

Helen

Senior Member
Messages
2,243
apologies if i sound a bit dense, brand new to gene expression. my question is: have any ME treatments resulted directly from work done in gene expression? Thanks.

I have no answer, but from experience that ME patients mostly get much better when they are on methylcobalamin injections at least one of the Swedish ME clinics genotype for MTHFR C677T and possibly also MTHFR A1298.

This trial, if accomplished, may result in what you are asking for:
https://app.etapestry.com/onlineforms/OMF/B12FolateTrial.html
I think it would have been a good idea if the MTR and MTRR SNP´s had been genotyped too. That would give a more complete picture of (some) possible genetic causes to an increased need for supplementating B12 and/or folate, as far as I can understand.

 
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Messages
15,786
apologies if i sound a bit dense, brand new to gene expression. my question is: have any ME treatments resulted directly from work done in gene expression? Thanks.
Well, based on a couple studies showing abnormally increased expression of ADRA2A in ME/CFS patients after exertion, I did try an ADRA2A inhibitor, yohimbe, and have very good results with it. It manages my OI better and much cheaper than Strattera did, and seems to have resolved my magnesium issues (constipation and muscle twitches).
 

Helen

Senior Member
Messages
2,243
Well, based on a couple studies showing abnormally increased expression of ADRA2A in ME/CFS patients after exertion, I did try an ADRA2A inhibitor, yohimbe, and have very good results with it. It manages my OI better and much cheaper than Strattera did, and seems to have resolved my magnesium issues (constipation and muscle twitches).

Did you just try the ADRA2A inhibitor, or could you also see a polymorphism that indicated you could have an upregulation in your 23andme test?
 
Messages
15,786
Did you just try the ADRA2A inhibitor, or could you also see a polymorphism that indicated you could have an upregulation in your 23andme test?
I couldn't see any polymorphism responsible for the regulation. But that was somewhat to be expected, since the ME/CFS patients had normal expression prior to exercise, and it only became upregulated afterward.