Wednesday, August 01, 2007

A Different Kind Of Gene...

No, I'm really NOT talking about Gene Kelly here...I just thought the picture would be *cute* in association with the latest genetic research findings regarding Multiple Sclerosis. (**blushing with obvious cuteness here**)

Joyce/Harkoo waaaaay over in Maine sent me an email two days ago wondering why I had not written a post about the latest "buzz" surrounding the new discoveries in MS research...I didn't really have an answer for her that would justify my neglect so, here it is. LOL Not the excuse, but the post, that is. I just assumed EVERYONE had already seen something about this buzz news...the information IS all over the papers and even the TV right now.

But, for those of you still living under that rock, I give you a post about the latest genetic findings in MS research. Of course, I must lie, cheat, and steal my way into providing this information (as always), so I've taken liberty to plagiarize from a website called . I'm sure they will be calling their lawyers soon to have me jailed! It's just THEIR website seemed to provide the most condensed and accurate information about this news. So here it is:

The study goes on to say (in case reading from a stolen picture that is somewhat blurred is difficult!):

Both studies involved scanning DNA samples from more than 20,000 MS patients and unaffected individuals in the U.S. and Europe, and looking for single nucleotide polymorphisms (SNPs), which are single-letter variations in a gene's DNA code. Published simultaneously today in the New England Journal (NEJM) and Nature Genetics, the studies demonstrate an association between MS and SNPs in two genes that encode interleukin receptors, proteins that serve as antennae on the surface of immune cells.

Both studies were supported by

  • NINDS and the National Multiple Sclerosis Society.

  • The Nature Genetics study received additional support from the National Institute of General Medical Sciences (NIGMS).

  • The NEJM study was also supported in part by the Penates Foundation.

They were conducted by overlapping teams of researchers that used different gene-hunting strategies. One team, which scanned the entire human genome for MS risk factors, was co-led by David Hafler, M.D., Professor of Neurology at Harvard Medical School and Brigham and Women's Hospital in Boston, Stephen Hauser, M.D., Professor and Chair of Neurology at the University of California in San Francisco, and Alastair Compston, FRCP, Ph.D., Head of the Department of Clinical Neurosciences at the University of Cambridge, U.K. The other team, which focused their search on a set of genes they considered potential risk factors for MS, was co-led by Jonathan Haines, Ph.D., Director of the Center for Human Genetics Research at Vanderbilt University Medical Center in Nashville, Tenn. and Margaret A. Pericak-Vance, Ph.D., Director of the Miami Institute for Human Genomics at the University of Miami. Drs. Hauser, Compston, Haines and Pericak-Vance participated in both studies.

MS typically causes limb weakness, vision loss and problems with coordination, and is the most common disabling neurological disorder of young adults. It's an autoimmune disease, occurring when the body's immune system mistakenly attacks a protective sheath around axons the delicate cables that nerve cells use to connect with each other. Various immunosuppressant drugs can reduce symptoms and slow the disease's course, but most MS patients become increasingly disabled with time.

The trigger for MS is unclear, though there's good evidence for an interplay between genetic susceptibility and some type of environmental factor. Having a relative, particularly an identical twin, with MS increases one's risk of developing the disease. In the mid-1970s, scientists discovered that human leukocyte antigens (HLA) account for some of this genetic susceptibility. HLAs are proteins displayed on all the body's cells to help the immune system distinguish self from non-self. A variant of the HLA-DRB1 gene, now widely accepted as the strongest genetic risk factor for MS, increases the likelihood of getting the disease up to four-fold.

Still, HLA does not fully explain the genetic basis of MS; researchers have long realized that other genes must play a role that has been difficult to detect. Some studies have pointed to other HLA genes, but neither of the two genes reported today belong to that category. Both genes encode receptors on the surface of T cells the immune system's mobile infantry that enable the cells to respond to regulatory, secreted proteins called interleukins.

"These are the first non-HLA genes to be unequivocally linked to MS," said Dr. Pericak-Vance. "They give us a new way of looking at the biology of the disease, and could be targets for therapeutic development".

Both studies searched for a link between MS and SNPs that were previously identified by the HapMap, an NIH-supported project to catalog genetic differences in human populations.

In the genome-wide association study, the first of its kind in MS, the scientists used gene chip technology to scan more than 500,000 SNPs. In total, they analyzed more than 13,000 DNA samples, a number of of them collected and stored by the Center for Genetic Studies at the National Institute of Mental Health (NIMH) and the U.K.'s Wellcome Trust Case Control Consortium. In the candidate gene study, the scientists scanned DNA samples from four large groups in the U.S, U.K. and Belgium, totaling more than 10,000 people.

Both studies revealed an association between MS and a single SNP in the gene interleukin 7 receptor-alpha (IL7R-alpha). The genome-wide scan also found two SNPs in the gene for interleukin 2 receptor-alpha (IL2R-alpha) linked to the disease. Both receptors are known to influence the way that T cells patrol the body for pathogens. IL2R-alpha has previously been implicated in other autoimmune diseases, including type 1 diabetes. Each of the SNPs linked to MS appears to increase the risk of developing the disease by about 20 to 30 percent. Even though that number might seem small, "it's the size of effect we expect to see for genes outside of HLA," said Dr. Haines. Multiple genetic variations, each carrying a small risk of MS, could combine with one another and with environmental factors to create a large risk, he said.

The scientists who conducted the candidate gene search also think they know how variation in the IL7R-alpha gene affects the IL7R-alpha protein. They found evidence that the MS-associated variant causes a reduction in the amount of the IL7R-alpha protein at the T cell surface. Less is known about how variation in IL2R-alpha might contribute to MS, but that protein is already being viewed as useful therapeutic target. In a 2004 study by NINDS scientists, 10 MS patients who were unresponsive to currently approved therapies showed improvement when treated with an antibody that blocks IL2R-alpha, developed to prevent rejection of organ transplants.

Finally, the genome-wide scan identified nearly a dozen other genes that could represent risk factors for MS. Some of the associations were relatively weak and some of the genes' functions are unclear.

"A major effort to understand the full complement of genes involved in MS will be necessary to completely understand the disease," said Dr. Hafler, adding that all of the data from the genome scan will be made publicly available for future investigations.

So, what does all of this mean for you and I?...the potential "carriers" of this genetic flaw? Well, unfortunately at this stage in the research game, NOT A WHOLE HELL OF A LOT. The genetic "stuff" (because I simply cannot type those big words!) they found only has a likelihood of linking MS to about 20% - 30% of the MS population. This STILL does not explain nor provide categorical markers for treatment.

I'm not trying to rain on these diligent scientist's parade...they certainly have done something big here. But until the exact formula for cause of MS is known, we will continue to experiment with these God awful medications that presumably will only SLOW the disease from progression mere percentages. And since the research done on most of the drug treatments has been conducted by BIG PHARMA COMPANIES, I certainly don't even trust their boasted "highs" of responses (which typically now only reach into the 60 percentile range...what about the remaining FORTY PERCENTERS WITH MS WHO ARE NOT BENEFITING FROM DRUG TREATMENTS?!?) But, as is usual, I digress. LOL

There IS some fascinating (and that is my standard here) research being conducted by a female researcher (I think out of Harvard...but since I can't even recall her name at the moment because MS HAS ROBBED MY FRIGGIN' MEMORY, who knows for sure??!!!), who is isolating 4 different types of MS lesion formation...of course done via AUTOPSY from the brains of deceased MSers...poor bastards.

ANYWAY...she is discovering we don't ALL have the same type of MS in our nervous systems and I'm not talking about RRMS vs. SPMS vs. PPMS. I'm talking about four different types of MS WITHIN these categories. It is speculated currently that these four different types of lesion/disease processes may be the culprit WHY we don't all respond the same to Interferons/Monoclonal Antibodies/Copaxone, etc. If it can be determined WHICH type of physiological disease process of MS an individual has, then medications can be cocktail tailored SPECIFICALLY FOR THAT INDIVIDUAL. Now *this*, my friends, is exciting.

I'm off now to get ready for work...sometimes I wish I were sitting in a research lab all day just futzing with stuff. But then again, our scientist friend of MS, Sara, over in England (who frequently comments here, but is currently on a wonder vacation in the States) might have some words of wisdom to share about just how "fun" research *futzing* might be! LOL


harkoo said...

Thank you for the comprehensive explanation of the recent findings. I heard about it in the New York Times on Monday in a simpler form. One thing that was of interest to me in your writing is that my mom had ms and she was an identical twin-that is the first time i have heard of the twin factor. Then i was diagnosed years later. Still so much to learn! What an odd club to belong to.

knicksgrl0917 said...
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Steve said...

scary for me. Both my wife's parents had ms. Eep!!

Miss Chris said...

Wow! That sure is a lot of info...I think I followed it all and it still comes down to the basics. They are reaching in hopes of getting some grasp on this disease, however small it may be. Oh well, I guess we have to take what we can get....without getting our hopes up though.
By the way, didn't knicksgrl get the message last time she commented on your site?

knicksgrl0917 said...
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