Biomarker research:medication response

[Jules A]

I’m not especially optimistic with regard to finding a “cure” for MS however the continued research does appear to be shedding some light on not only the precipitating factors and our susceptibility but what is more interesting to me in this article is the mention of the individualized reaction to medications we presently use to treat MS. (note: ADME=absorption, distribution, metabolism and excretion)

Sad that they identified the human leukocyte antigen (HLA) connection to MS almost 40 years ago and this angle of research is only taking off in recent years but I guess better late than never.

“The Multiple Sclerosis Genetic Burden (MSGB) Score. The GWAS approach opens possibilities for individual genetic risk score computations. By the end of 2011, the number of genomic regions associated with MS susceptibility was more than 50. With additional GWAS currently being performed, and meta-analysis compiling an ever growing number of studies, the count of MS associated variants will most likely surpass 100 in 2013.

The second avenue by which biomarker research is likely to impact MS care is in the prediction of therapeutic response. This is an area of intense research and represents a shift in the previously widespread notion (particularly in the pharmaceutical industry) that all patients are equally likely to respond to a given drug. Recent data on the architecture of the human genome have unequivocally shown that there is abundant genetic variation between individuals that could account for differential ADME profiles, drug metabolism, transport, safety, and ultimately, response to pharmacological agents.”

http://onlinelibrary.wiley.com/doi/1...2.01134.x/full

[Sequoia]

This is an interesting article, Jules!

However, it would seem to belong in the newly-created "New Treatments and Trials" sub-forum, or at least the "Medications & Treatments" forum. Perhaps a Moderator will come along and move it.

[Tawanda]

Hey, I'm a part of that genome study! Since M.S. runs rampant in my family, we thought we could at least use our misfortune to help future generations by having our DNA disected!

Haven't heard any news in awhile, so I'm glad you pointed this out to me. It's crummy about that 40 year hold up, however. What up with that?

Thanks for the update, Jules! I remain hopefull that we will nail down a cure for this MeSs in our lifetime. That might be optomistic, but you have to walk before you can run and it sounds like at least we're finally walkin', at least.

[Jules A]

This is an interesting article, Jules!

However, it would seem to belong in the newly-created "New Treatments and Trials" sub-forum, or at least the "Medications & Treatments" forum. Perhaps a Moderator will come along and move it.

I'm glad you enjoyed it. Since it really isn't a treatment, trial or medication I'd prefer it here where it might get more visibility. Although I have to say I'm always kind of disappointed by what seems to be the lack of interest in the research articles that I post occasionally. We really need to be educated and act as our own advocates in partnership with medical professionals for optimal outcome, MS or whatever the disease process, imo.

I'd love a MS/Genetics section where we could share insights and updates. I wonder if that is something the mods would consider as it is a crucial and exciting area of science right now. Hmmm you just gave me an idea.

[Tawanda]

I'm glad you enjoyed it. Since it really isn't a treatment, trial or medication I'd prefer it here where it might get more visibility. Although I have to say I'm always kind of disappointed by what seems to be the lack of interest in the research articles that I post occasionally. We really need to be educated and act as our own advocates in partnership with medical professionals for optimal outcome, MS or whatever the disease process, imo.

I'd love a MS/Genetics section where we could share insights and updates. I wonder if that is something the mods would consider as it is a crucial and exciting area of science right now. Hmmm you just gave me an idea.

I, for one, don't want to live with this disease forever. I tried to think of a reason why these posts generate so little interest. Maybe it's because real scientific progress has been so excrutiatingly slow when it comes to finding a cure for M.S. I think we are just are waiting for a magic bullet to come along and fix us! I can honestly say I, for one, have been guilty of this...

Thank you Jules and all you other research hounds at MSW who make the effort to educate those of us who are not as inclined to do our own homework.

[BigA]

It just takes too long for exciting possibilities to become treatmets, if they ever do. It's guaranteed to be a downer. Idividual response to DMDs is exciting, however if you think about it, people are already doing that - it just takes a few exacerbations to find out.

It's just not that exciting until it becomes at least a phase II trial.

BTW, is there a link to the study?

[Jules A]

Thanks so much for your responses.

Big A, it isn't a study. The article I added in my op is a meta-analysis which is a compilation of research where the authors basically summarize published data.

It covers many of the different genetic implications of MS which I believe is the key to better understanding this disease and one of my biggest pet peeves in the MS community.

Without acknowledging, accepting and addressing the genetic components of MS how can we make progress?

[Tawanda]

Without acknowledging, accepting and addressing the genetic components of MS how can we make progress?

With a mother, 3 cousins and myself all members of "Club M.S." I'd like to see anyone tell us with a straight face how little genetic components matter when it comes to developing M.S. It's not like I LIKE it, but numbers don't lie.

I don't relish the idea of ever telling anybody, "I told you so", especially since I have a daughter to worry about myself, but facts are facts. If we ever want to beat this thing, we need to be honest about where the data is leading (and take emotion out of the equation).

Learning as much as possible about the "enemy" is the best way of defeating it. Isn't that the logical thing to do?

[lusciousleaves]

Biotech has always been a big interest for me, so these genetic investigations I find incredibly interesting and informative. They shed more light on the stage of progress in research than many of the reinterpreted articles written about them.

As far as what has taken so long since the HLA connection was made 40 years ago, it's that technology didn't allow looking further until new testing capabilities came about. Many new technological developments came about in the 80s, which spurred the human genome project. Those fields are still growing by leaps and bounds. I'm guessing that the bigger holdup today pis funding and manpower rather than technology.

Thanks for posting, Jules. More quality reading to digest on a slower day. Adding to the bookmarks. I'm excited to hear about this new "genetic burden" idea. What a great approach.

I've gotten my genome mapped through 23andMe, but I can tell you they haven't caught up to these new GWASs. The identified SNPs aren't particularly ready for using as a diagnostic tool and I'm assuming it will be quite some time before they're widely accepted.

I also find it exciting they're connecting genetic markers to how well pharmaceuticals are processed by the body. Having mine testing opened up some info as to why I don't respond well to certain meds.

There are labs that do more in depth analyses on a person's genetic metabolic makeup, also providing software to the physicians ordering the testing. It allows them to keep tabs on which meds will work best for which patients and which selections are likely to interact badly with currently prescribed meds.

This field is going to boom, and I feel is going to improve healthcare tremendously.

The testing done through the company I used will give results on whether or not a person is likely to respond well to Betaseron and similar meds.

[Jules A]

There are labs that do more in depth analyses on a person's genetic metabolic makeup, also providing software to the physicians ordering the testing. It allows them to keep tabs on which meds will work best for which patients and which selections are likely to interact badly with currently prescribed meds.

This field is going to boom, and I feel is going to improve healthcare tremendously.

Thank you for writing! It makes good sense to me in light of the knowledge we already use for example with psychiatric medications that are metabolized by P450 enzymes.

It is widely accepted that certain races are more likely to have a reduced capability to process/use/excrete certain medications so I really think it is time we expand that line of thinking.

[Tawanda]

It allows them to keep tabs on which meds will work best for which patients and which selections are likely to interact badly with currently prescribed meds.

This field is going to boom, and I feel is going to improve healthcare tremendously.

The testing done through the company I used will give results on whether or not a person is likely to respond well to Betaseron and similar meds.

O.K., I realize I am throwing spaghetti at the wall here, but hear me out. Out of my 3 cousins, there was one who was doing remarkedly better than the others. One cousin was diagnosed before DMDs and was on nothing...she was doing the worst. I had ten years of guinea pig cousins to study (basically persons who presumably have a similar DNA) and decided based on my limited "study", that Avonex would be the drug for me. My cousin who was doing the "best" had managed to keep his job and work out at the gym most days for over a decade despite having M.S. at the time I was diagnosed In a nutshell, I still have no mobility issues after 8 years of diagnosis while my M.S. mother was in a W/C almost immediately. I always wonder if Avonex had been around back then, would she still be here?

I am not advocating for Avonex in any way. In fact, it might be the worst choice for someone else with M.S. I'm also not saying it's a miracle drug either (I still feel like poop)! I am just blessed that I can walk, talk, exercise and drive/do errands for that small part of the day when my fatigue isn't busy ruining my life. My mother was "frozen" and we had to reposition her throught the course of the day and my Dad carried her to bed every night. Now that stinks a lot worse than the life I am living!

[Tawanda]

BOTTOM LINE: WE NEED SOME COOL, HARD CASH!

I'm guessing that the bigger holdup today pis funding and manpower rather than technology.

I agree totally. When President Roosevelt was thought to have Polio, all kinds of money was dumped into finding a cure for it. It was heavily publicized with all kinds of footage of little children in iron lungs and such. Low and below a miracle happened. In almost record time, a vaccine was develop eliminating all kinds of suffering.

Somehow I still don't think our M.S. community has managed to convey how devastating this disease is, and if it's not "that bad", why would anyone want to donate money to it?

If you could throw enough money into a cause, it's amazing what happens! It's a bummer that our cause seems to be so far down on the list as M.S. is still considered an "orphan disease".

[lusciousleaves]

Thank you for writing! It makes good sense to me in light of the knowledge we already use for example with psychiatric medications that are metabolized by P450 enzymes.

It is widely accepted that certain races are more likely to have a reduced capability to process/use/excrete certain medications so I really think it is time we expand that line of thinking.

Couldn't agree more. According to the lab that does this testing (insurance picks up the cost as well), more than 50% of the population have variations that change how their bodies process meds. It's extremely common. A person can have super-fast processing variations on down to super slow. I believe they test for close to 9 pathways.

Using their system, a doc can input what meds the patient is currently prescribed and it can help them select and tweak the combinations and dosages to optimize their treatment and best of all - it will cut down on the number of bad drug reactions.

Unfortunately, the clinic I use doesn't have any way of making use of that information. Their computer system is the limitation. I guess there is no field for entering genetic metabolic pathway variations. Ha!

Being in the healthcare field yourself, I'm wondering if you may have caught wind of any of this and if there are any plans to implement these new discoveries into the databases. Any news from the inside?

[lusciousleaves]

O.K., I realize I am throwing spaghetti at the wall here, but hear me out. Out of my 3 cousins, there was one who was doing remarkedly better than the others. One cousin was diagnosed before DMDs and was on nothing...she was doing the worst. I had ten years of guinea pig cousins to study (basically persons who presumably have a similar DNA) and decided based on my limited "study", that Avonex would be the drug for me. My cousin who was doing the "best" had managed to keep his job and work out at the gym most days for over a decade despite having M.S. at the time I was diagnosed In a nutshell, I still have no mobility issues after 8 years of diagnosis while my M.S. mother was in a W/C almost immediately. I always wonder if Avonex had been around back then, would she still be here?

I am not advocating for Avonex in any way. In fact, it might be the worst choice for someone else with M.S. I'm also not saying it's a miracle drug either (I still feel like poop)! I am just blessed that I can walk, talk, exercise and drive/do errands for that small part of the day when my fatigue isn't busy ruining my life. My mother was "frozen" and we had to reposition her throught the course of the day and my Dad carried her to bed every night. Now that stinks a lot worse than the life I am living!

I'm glad you're doing so well, and think it was a smart way to go about choosing your path. It seems to be working on the surface. I think it's wonderful that you and your family are participating in the genetic research studies. What a wonderful way to give back to the researchers.

The funding issue . . . not touching that with a ten foot pole. It's a good way to get a thread locked.

[Jules A]

There are limited new discoveries that I am privy to in my field right now even at a large inner city teaching hospital. In general psychiatry is often a bit of a neglected area although I did recently attend a lecture that encouraged genetic testing prior to treating with the highlighted therapy.

It was in the context of a possible connection between l-methylfolate and depression which interestingly enough is also being hypothesized to have inflammatory components. The data indicated that up to 70% of people have a genetic mutation that decreases their ability to convert folic acid to l-methylfolate.

Below is a link to an article that I thought was interesting on that topic as well as a link to a genome testing company one of the other practitioners suggested as an inexpensive service. FWIW I don't know anything about Inherent health 5-line genomic testing it was just something that was mentioned.


http://www.psy-world.com/739-744_100...tahl_stamp.pdf


http://www.ilgenetics.com/content/ne.../q/news-id/241