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Julie  Stachowiak, Ph.D.

GIFT15: A "cure" for multiple sclerosis?

By August 26, 2009

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Trust me, I would love nothing more than to tell you all, "Hallelujah! This is IT! The cure is here!" And maybe I will be able to write those words someday, maybe even someday soon. But I can't do it quite yet. Don't get me wrong, GIFT15 is exciting, cutting-edge stuff, full of possibilities and definitely something we should all keep an eye on.

Let's take a look at what we have with GIFT15:

From what I can tell, this approach is similar to some of the experimental MS vaccine candidates that I wrote about, in that it is using components of a person's own immune system to stop the damage caused by MS and the process behind the disease. What the researchers are doing is:

1) Giving mice experimental autoimmune encephalomeylitis, which is the animal "equivalent" of MS. This is the standard way that most animal trials of MS treatment or investigations into causes of MS is conducted.

2) They then are isolating some immune cells from these mice, namely B cells, and putting them in a petri dish.

3) The researchers proceed to "sprinkle" this funky new protein, GIFT15, on these like fairy dust. They made GIFT15 in the laboratory by fusing GSM-CSF and interleukin-15, two proteins that usually act in the immune system to stimulate activity (it is unclear to me if these proteins were also derived from the individual mice and used only on their B cells, or if the GIFT15 is not as specific to the individual as the actual B cells, which I think is the case) . Interestingly, when these proteins are fused together in the lab, they are shown to have the opposite effect on the B cells that they come into contact with and "downregulate" their activity, kind of like a natural immunosuppressant.

4) The researchers then stuck the new GIFT15Breg cells back into the same mice that they came from, and voila! all signs of MS (well, EAE, to be precise) disappeared as these new cells went to work "calming down" the immune system. Remember, MS is an autoimmune disorder, which means a person's own immune cells are attacking his or her body, namely the myelin surrounding the nerve structures. Which exact cells are doing this damage is still a matter of great (and lengthy) debate.

There you have it. Exciting stuff! However let's remember that mice are not humans and EAE is not multiple sclerosis. It doesn't always act the same. Just think about it - if there are 4 different types of MS and each one of us experience MS differently, with different symptoms and severity, it doesn't compute that something that worked in a couple of mice would work in all people with MS. Again, it is all exciting, and we will keep an eye on GIFT15 as it progresses through the research process.

I'll admit it, the science involved in this experiment stretches (okay, exceeds) my grasp of the specifics of immunology. If you are interested in going in deeper, here is the link to the abstract: A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties.

If you are interested in other novel approaches to manipulating a person's own immune system, check out these articles:

Comments
August 26, 2009 at 11:01 am
(1) yourverity says:

It is my personal belief that MS is NOT ones own immune system attacking itself. I feel that it is a weak immune system that does not function correctly because of a leaky gut, low hormones and the inability to grown the needed cells for proper nerve function (no matter what the trigger is/was). EAE is (in my opinion) not close to what MS is in humans, therefore I don’t think GIFT15 shows any promise.

“If people keep digging for gold 500 miles away from where gold is they will never find it”

-Allen Bender-

August 26, 2009 at 11:39 am
(2) Martin says:

Julie and All, note that unfortunately NeuroVax, while having been shown to be extremely effective in many patients, is unfortunately dead, as the company making it went bankrupt last year under the stress of the general economic downfall and had to halt all trials.

I feel an urge to be cynical and have to note that the money earned by a day less of Iraq war would have probably been plenty of support to keep a large rolling…but it’s all a matter of where we put our priorities…

August 26, 2009 at 11:41 am
(3) Martin says:

I meant to say “plenty of support to keep a large TRIAL rolling”, of course…

August 26, 2009 at 4:32 pm
(4) Rusty Bromley says:

Dr. Stachowiak,

We at the MRF appreciate the measured response and dissection of the science in this “cure” for multiple sclerosis. Too often I read mainstream media articles that exaggerate the importance of a scientific discovery and give false hope to multiple sclerosis patients. Please continue your good work in communicating research news to a lay audience.

We at the MRF have always tried to provide an appropriate context and perspective in our progress reports are trying to do the same with our new blog (http://blog.myelinrepair.org) — I would appreciate your comments and feedback on our research and communications. Please contact me at my email address.

August 27, 2009 at 11:47 am
(5) Karen says:

I disagree with yourverity…i have MS…I was diagnosed Feb of this year….but i’ve had it for at least 7 years…a weak immune system is the last thing that can be said about me….i couldn’t even catch a frickn everyday cold…if anything my immune system is so damn good it has nothing better to do than attack my own body!!!

August 28, 2009 at 4:53 am
(6) Janus1 says:

I have no formal medical training. I was diagnosed with MS 35 years ago. I believe it’s a mitochondrial DNA malfunction. Read my argument in support of the Viking Hypothesis at:
http://www. aspects.net/~janus/MSframes.htm/viking_ms.htm

August 28, 2009 at 10:11 am
(7) yourverity says:

“I disagree with yourverity…i have MS…I was diagnosed Feb of this year….but i’ve had it for at least 7 years…a weak immune system is the last thing that can be said about me….i couldn’t even catch a frickn everyday cold…if anything my immune system is so damn good it has nothing better to do than attack my own body!!!”

Karen, no disrespect but you having just been diagnosed in Feb. of this year doesn’t give you much time to have really researched this disease. Right now I am sure you are going strongly by what the Docs are telling you and showing you. I was diagnosed 15 years ago and some say I have had it for almost 30 years now. I have done a lot of research and met with a great number of doctors on this. There is a growing number of people (doctors, MSers, etc…) that think this thing is not over active and the more they look into it the more it makes sense. Please do you own research and do not believe everything that the so-called “specialists” are feeding you. There is too much at stake if this disease is to be discovered as NOT and over-active immune system.

August 30, 2009 at 10:25 am
(8) dee says:

Thanks for your summary of gift15 Julie, very well explained. I continue to spend a lot of time researching things and have come across the idea that low levels of uric acid are found in people with ms and that people who have gout(from high levels of uric acid) are highly unlikely to ever get ms…have you ever investigated this idea? Thanks for your insight.

September 2, 2009 at 12:29 pm
(9) TLH74 says:

I’m curious of your thoughts on CCSVI?? A very interesting read at thisisms on the subject. Do you think this could be something to get excited about??

September 5, 2009 at 2:20 am
(10) Ryan says:

Yourverity…

Your arrogance is pathetic. Nothing ruins an argument more than “I’ve got this much experience, listen to me and believe all I say.” Congratulations on completely ignoring her point that her immune system is too strong though. The people who claim to know the most are often times the ones who know the least. I count you as one of them.

September 5, 2009 at 7:30 pm
(11) pat says:

I agree with you Karen.. I like you was diagnosed this February.
Yourverity, Just because someone was recently diagnosed doesn’t nessarily mean that they haven’t been researching the issues that might have plagued her for years. I was diagnosed this February after having a positive mri last year. I was told that I didn’t have it, given tegratol and sent home… for years I have had issues for years, I have researched. Like Karen, I haven’t had a cold or even the sniffles in years…
I told the doctors that i had it! You don’t know the woman or her MS! My immune system is so over active, that even I can’t live in my own body! Lymes disease, Ra and Ms all at once.. I have lived this disease! I lost everything because of it.. I don’t take ANYTHING at face value… because you have had it for 30 years your now the specialist? I know people that have had it for 10 and are wheelchair bound.. Your MS is probably as benign as your myelin deficient brain. Your probably one of the idiots that say “it’s a livable disease”.
For some , yes for others, are you friggin kidding me.. My girl friend calls me everyday day expressing her wish to take her own life!. Speak for your damn self, but don’t speak for me ,for Karen or any one else that has to deal with this .
What the hell do you know? My God I haven’t been so angry since I found out I had it!

September 9, 2009 at 11:35 am
(12) yourverity says:

Ryan and Pat,

I do not make comments to call names or get in a battle, I was just stating that I think everyone one needs to do their own research and then some more research and then some more. I never said I was a specialist I just said my opinion thus far. Without someone looking at something different they may never find the answer.

If you guys feel you can only get your points across by calling those you may disagree with names then I say I can’t wait to read some more or your great creativity.

It’s your kind of thinking that gets progress no where.

October 16, 2009 at 10:54 pm
(13) Steven W. says:

I agree with Pat wholeheartetly!!! Who are you to tell me my MS isn’t MS but a weak immune system, bull@#%$!! YOu come and live my life for awhiile and see if you like it. I don’t even see myself living for 30 more years because of this damn disease, let alone being able to argue about t after having the disease for 30 years. You are pathetic.

September 29, 2010 at 4:29 am
(14) Hayden says:

I have ms, like all of you, and I look at every possible cure, not because im sure they will find one, but because this is my life and nothing will change with that one, and the only hope is to life it the most positive I can, I fight though all I can, try to be positive try to move on, and just as most people do with god, I believe there will be a cure and I can do nothing but move forward. So when reading peoples posts, well; I only missed one day of elementry school from k-6 of sickness and only one from 7-12, I still never feel I get sick! Diagnosed at 21 I have seen the stem cell stuff… even saw the guy on good day america… that brought me hope, and as long as I am not sure on what the cause/cure is I will listen to everyone without saying any of you are wrong… we think we know but we still have no idea… the mouse thing is hope… stem cell … hope.. so much hope and until I am cured of MS I will exhibit noting but hope… there is nothing in life worse then having no hope, dreams, faith and being filled with depression, I was sad for a week, and at times I am filled with sorrow, why me? I then realize it has done nothing to help me and I have to better my self, I have to do all I can do which is to move forward, and I hope everyone with MS does the same, beacuse sometimes when you wish, it does come true, but at the end of the day if it is not cured and you are still happy in life despite your challanges, just remember you are only that much stronger, and you can only live your life the best you can.

November 12, 2010 at 2:48 am
(15) nurah redi says:

There is no news about GIFT15 for more than one year.

Is there any trial for this material?

Any body who knows about it ?

January 11, 2013 at 10:15 pm
(16) Moutih Rafei says:

Dear all,

it is exciting to hear you all discussing EAE, MS, GIFT15 and its therapeutic effects. In fact, EAE is not MS per se but rather an induced MS-like disease to try and replicate some of the main pathologies we see in humans. In simpler terms, we stimulate the immune system to recognize a protein expressed on the surface of neurons. This is why MS is considered a disregulated immune-based disease. So far, no one knows what causes MS. Some say it is a bacterial or viral infection displaying proteins similar to those expressed on our neurons, other say it is genetic or related to diet or low exposure to sun rays. The end result is: the disease is immune-based but triggered by an unknown event. What GIFT15 does is reprogramming naturally occuring B cells (usually there to produce antibodies) into cells capable to repressing autoreactive MS-specific T cells via the secretion of immunesuppressive soluble factors and cell-cell contact. We have now preliminary data showing that the human GIFT15 can do the same to human B cells in vitro. Unfortunately however, this is how far we can go in pre-clinical models. The file of GIFT15 is now in the hands of funding and governmental agencies. If these agencies are not willing to put millions and time for development, this compound will unfortunately never make it to the clinic. Let’s be optimistic for the future.

Dr. Rafei

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