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The Open Medicine Institute is fostering a new health care model by integrating direct patient involvement with a multi-disciplinary, big data technology approach to advance the understanding of complex diseases and directly improve outcomes. Linda Tannenbaum, Executive Director of the Open Medicine Institute

The Open Medicine Institute announced today they’ve received  over $1,000,000 to investigate the genetic  underpinnings of chronic fatigue syndrome (ME/CFS) and  explore new treatments.  One grant from the Edward P. Evans Foundation will fund most intensive exploration of genes and gene expression yet in this  disease.  Another  from the Neuro-Immune -Disease- Alliance ( NIDA) will explore a promising herbal treatment using molecular profiling.

Gene Study

OMI-MERIT-Genome

The OMI gene study will take a deep look at previously unexplored portions of the genome that impact the immune system

The gene study is particularly gratifying  given the mounting evidence that, even with all its presumed subsets, chronic fatigue syndrome has a very strong genetic component.

Using newly developed techniques never applied to ME/CFS  and featuring one of the top investigators in  the field,  the Evans Foundation grant will fund intensive investigations into the HLA regions of the genome, methylation and  other aspects as well as whole  genome sequencing.

Bedrock of the Immune  System- The HLA Genes

When invaders enter the body they’re met by antigen presenting cells (dendritic cells, macrophages,  some B-cells, etc.)  that promptly gobble them up and then like warriors displaying trophies put a bit of them on the outside of their cells.  They then swim to  the lymph nodes so that T-cells can have a looksie.  If the T-cells decide the APC’s have found a pathogen they mount an immune response that usually wipes it out.

HLA

HLA’s control which parts of pathogens are presented to the immune system.

That part of the cell that recognizes and then mounts the viral proteins  on its surface is the HLA antigen.  If the HLA displays  the wrong part  of the pathogen or doesn’t display  any part of it,  the pathogen goes on its merry way unimpeded by a major branch of the immune system.  Without those little HLA messengers  we’d be at the mercy of the pathogens in our midst.

HLA’s also encode portions of the complement system (one part of which is activated in ME/CFS), protect against cancers and may be involved in autoimmune disorders.

Several studies have suggest HLA problems may be present in ME/CFS.  A 2011 study suggested HLA deficiencies were responsible for the low natural killer cell cytotoxicity in this disorder and a  2005 study suggested ME/CFS was associated with a specific HLA genotype.

The HLA genes, with their huge impact on immune functioning, are of major interest but the malleability that allows them to recognize virtually any pathogen, has made this portion of the genome particularly hard  to characterize.

Enter Ron Davis – Uber Genome ‘Techonologist’

Enter Ron Davis of Stanford, Director of the Genome Technology Center at Center, of the pre-eminent geneticists of our times.  More than just a geneticist, Davis is an inventor who holds over 40  biotechnological patents and has authored over 400 papers. The winner of the $500,000 2011 Gruber Genetics prize for his breakthroughs in the ‘development and application of recombinant-DNA techniques, if Davis can’t find a tool to do what he wants, his team simply develops one.

genome-technology

If Ron Davis and his lab don’t have a tool to explore the genome….they create one

Upon winning the Dickson Prize, Davis was cited for his “great positive impact on a broad swath of biomedical research”. The Dickson Foundation noted that he and his  “students, postdoctoral fellows, and technicians in his laboratory have developed many of the techniques currently used in academic and industrial biotechnology laboratories”. Davis is clearly a new and very important asset to the ME/CFS research community.

THe HLA technology being used is newly developed and highly touted and particularly applicable since HLA codes for the highly variable, immune-related region of DNA.  Both of these characteristics make them more likely than routine sequencing to show something of value in ME/CFS.  Dr. Kogelnik

Now Kogelnik and Davis will be using their newly minted technology to explore a  heretofore obscured part of our genome.  Both Kogelnik and Davis believe this area is ripe for exploration in ME/CFS and if their hunch is correct, this study could open an entirely new window on this disease.

Methylation

Given the critical role of DNA methylation in gene expression and cell differentiation, it seems obvious that errors in methylation could give rise to a number of devastating consequences, including various diseases. The Role of Methylation in Gene Expression.

Methylation simply adds a ‘methyl group’  to strands of DNA but that little addition can change everything because that methyl group can determine whether an gene will express itself or not.  The finding  that highly methylated regions in the genome are mostly silent gave way to the realization that methylation played a key role in gene expression.

methylation

Through its ability to turn off gene expression methylation can effect many areas of the body

Epigenetics looks at whether something (aka methylation) came along to change the expression of the genes we are borne with. On May 16th, the CFIDS Association of America’s webinar on epigenetics will explore whether methylation or other processes have turned on or off key genes that exist at stress -immune response interface. McGowan, the CAA’s researcher, believes epigenetic mechanisms are disrupting immune responses in ME/CFS.

Methylation has also started off on a preliminary but promising foot  with a 2011 CDC study suggesting that methylation and other processes may impair serotonergic neurotransmission, an interesting finding given the CFIDS Associations Biovista project finding that two serotonin effecting drugs (not yet named) may be useful in this disorder.

The OMI study is going to blast the field of methylation in ME/CFS wide open. With their focus on HLA and methylation genes  the OMI will be taking a deep dive into two virtually untouched and very promising areas in ME/CFS genetics.

Others

Beside the HLA and methylation projects, whole genome sequencing will be applied  to some individuals and many others will be the recipients of a focus on  parts of the genome (inflammatory, immune, signaling. etc.)  Kogelnik believes are in play in ME/CFS.

One part of the project will feature one of Kogelnik’s favorite techniques; contrasting  the results of responders to Rituximab and valganciclovir and non-responders in an attempt to understand why these drugs area working in some individuals and not others. Finding genetic differences potentially gives Kogelnik a straight line to a biomarker.

By the time the study is done approximately 1,000 ME/CFS patients will have taken part. This kind of  data gathering on such a  grand scale is rare in ME/CFS.

Moringa oleifera Trial

The OMI will also conduct the first of what will hopefully be a series of studies  examining  untested but promising natural therapies.  Called the ‘miracle tree’ Moringa oleifera  has been proposed to having antibiotic, antitrypanosomal, hypotensive, antispasmodic, antiulcer, anti-inflammatory, hypocholesterolemic, and hypoglycemic activities but few studies have been done.

Moringaoleifera

Medical researchers are very interested in Moringa olivera but few human trials have been done..

This is what Dr. Kogelnik had to say about the Moringa trial.

We had heard a number of promising but VERY anecdotal stories of recovery with this substance.  Like many natural (unregulated) substances it was completely untested scientifically in ME/CFS.  That combined with the claimed boosting of NK cell function (and the relatively low cost of doing a pilot with this substance) made it a great first target to illustrate how low-budget science can also be beneficial in this field and needs to be done.  We hope to apply this method to other potential candidate substances as we move forward with MERIT.

Conclusions

The Open Medicine Institutes ambitious OMI-MERIT program for ME/CFS is off to a good start with this major grant.  They aim to speed up the pace of ME/CFS research and treatment findings by applying a ‘big data’ approach. Expect more from the OMI soon.

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