Multiple sclerosis successfully reversed in animals

Aug 11, 2009
This is Dr. Jacques Galipeau of the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University. Credit: Claudio Calligaries/McGill University

(PhysOrg.com) -- A new experimental treatment for multiple sclerosis (MS) completely reverses the devastating autoimmune disorder in mice, and might work exactly the same way in humans, say researchers at the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University in Montreal.

MS is an autoimmune disease in which the body's own immune response attacks the , almost as if the body had become allergic to itself, leading to progressive physical and cognitive disability.

The new treatment, appropriately named GIFT15, puts MS into remission by suppressing the immune response. This means it might also be effective against other like Crohn's disease, lupus and arthritis, the researchers said, and could theoretically also control immune responses in patients. Moreover, unlike earlier immune-supppressing therapies which rely on chemical pharamaceuticals, this approach is a personalized form of cellular therapy which utilizes the body's own cells to suppress immunity in a much more targeted way.

GIFT15 was discovered by a team led by Dr. Jacques Galipeau of the JGH Lady Davis Institute and McGill's Faculty of Medicine. The results were published August 9 in the prestigious journal .

GIFT15 is composed of two proteins, GSM-CSF and interleukin-15, fused together artificially in the lab. Under normal circumstances, the individual proteins usually act to stimulate the immune system, but in their fused form, the equation reverses itself.

"You know those mythical animals that have the head of an eagle and the body of a lion? They're called chimeras. In a lyrical sense, that's what we've created," said Galipeau, a world-renowned expert in cell regeneration affiliated with the Segal Cancer Centre at the Jewish General and McGill's Centre for Translational Research. "GIFT15 is a new protein hormone composed of two distinct proteins, and when they're stuck together they lead to a completely unexpected biological effect."

This effect, explained Galipeau, converts B-cells -- a common form of white blood cell normally involved in immune response -- into powerful immune-suppressive cells. Unlike their better-known cousins, T-cells, naturally-occurring immune-suppressing B-cells are almost unknown in nature and the notion of using them to control immunity is very new.

"GIFT15 can take your normal, run-of-the-mill B-cells and convert them -- in a Superman or Jekyll -Hyde sort of way -- into these super-powerful B-regulatory cells," Galipeau explained. "We can do that in a petri dish. We took normal B-cells from mice, and sprinkled GIFT15 on them, which led to this Jekyll and Hyde effect.

"And when we gave them back intravenously to mice ill with , the disease went away."

MS must be caught in its earliest stages, Galipeau cautioned, and clinical studies are needed to test the treatment's efficacy and safety in humans. No significant side-effects showed up in the mice, he said, and the treatment was fully effective with a single dose.

"It's easy to collect B-cells from a patient," he added. "It's just like donating blood. We purify them in the lab, treat them with GIFT15 in a petri dish, and give them back to the patient. That's what we did in mice, and that's what we believe we could do in people. It would be very easy to take the next step, it's just a question of finding the financial resources and partnerships to make this a reality."

Source: McGill University (news : web)

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User comments : 17

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Biotele
3 / 5 (1) Aug 11, 2009
B-cell suppression with rituximab apparently reverses RA and is being tried to treat MS.

http://www.thenat...916/1036

frajo
4.4 / 5 (7) Aug 11, 2009
"appropriately named GIFT15" --
Yes, for English speakers. The German meaning of "gift" is poison.
Soylent
5 / 5 (1) Aug 11, 2009
Same here in Sweden(pronounced 'jift').
Zenmaster
5 / 5 (1) Aug 11, 2009
"You know those mythical animals that have the head of an eagle and the body of a lion? They're called chimeras..." - They're called Gryphons.
carol7358
4 / 5 (3) Aug 11, 2009
"You know those mythical animals that have the head of an eagle and the body of a lion? They're called chimeras..." - They're called Gryphons.
You are both right. Chimera is the generic term for such mythological creatures. Gryphon is the specific term for the
eagle/lion combination.
tallison
4 / 5 (1) Aug 12, 2009
There is no comment here on the validity (or lack thereof) of the mouse model for MS used in this work. I seem to recall reading that such models were far from accurate representations of the disease as it occurs in human beings (something like: mice don't get MS, so let's approximate it with this gene knock-out). Am I mis-remembering that? This result is interesting, in terms of technique, regardless, but it's a bit frustrating that everything has to be framed in terms of a disease, regardless of the actual relevance, and it tends to offer false hope to those who actually suffer from said disease. Can anyone reassure me that that is not the case, here? (I'm not blaming anyone, except maybe the sloppy/overly rosy reporting, here -- I understand why it helps to frame ones research in terms of potential clinical relevance, but let's not fool ourselves -- or those who suffer from the diseases.)
djoseff
not rated yet Aug 12, 2009
Great article, and fantastic research. This likely represents a lot of bench work and exciting, out of the box reasoning. Rituximab is B cell depleting and now used in a wide range of diseases of presumed excessive immunity, and since it doesn't deplete (non-CD20 expressing) plasma cells some immunity may be retained, but it does deplete B cells for months. This research is exciting in that the returned B cells now moderate the disease, leading to all sorts of interesting questions that hopefully will be answered soon. Thanks to bench researchers everywhere!
fixer
1 / 5 (1) Aug 12, 2009
Forget it! Having a supressed immune system allows every kind of bacteria to invade your body without resistance.
It's a kind of manufactured AIDS, a lousy way to die!
Back to the drawing board...
El_Nose
not rated yet Aug 12, 2009
i agree with fixer -- does anyone else have a problem with this -- one dose and your immune system is suppressed and the disease is gone, so one dose suppresses your immune system FOREVER. Does this suppressed immune system carry to children -- all it seems to take is a few "chimera protiens" in your blood stream and it has a catalyst like effect where the effect is permenant but the catalyst stays intact.

I love advances in biology and chemistry with protien synthesis and us 'human' learning and naming everything we find but i guess i watched to many zombie movies as a kid and it scares the bejesus out of me to think we might one day accidentally introduce a material that kills us as a species 20 generations later, by accident.

----
PLEASE RESPOND TO THIS QUESTION IF YOU ARE KNOWLEGDABLE

I my old science courses we were told that women essentially were born with all the eggs they would produce in life already formed or staged ready for their bodies to develop and a hormone to push them out one at a time. Now after more courses I realize that no cell in the body lives for that long.... so is this true in some fashion?? or (hypothetical) if humans could stay in our twenties and thirties say 20 extra years could a woman still have eggs to reproduce??

i know the question is off topic but i figure people in biology would come to this article

Thanks in advance
Lord_jag
1 / 5 (1) Aug 12, 2009
Wiki:
The term chimera has also come to mean, more generally, an impossible or foolish fantasy.

Maybe that is the best term?
nxtr
5 / 5 (1) Aug 12, 2009
Ironically not funded by the MS fund-sucking machines. But still great news.

I think the immuno-suppression is only temporary while the disease is overcome. It does say no serious side-effects. A complete lack of immunities I would call a side-effect.
tkjtkj
not rated yet Aug 12, 2009
re:
.. It does say no serious side-effects. A complete lack of immunities I would call a side-effect.


Perhaps the mice were not asked the right questions ..

tkjtkj@gmail.com

bkeepergd
5 / 5 (1) Aug 12, 2009
fixer, some of us who have been suffering with MS for 20 years might be willing to take a chance on suppressing our immune systems. My body, my life, my decision. A "lousy way to die"? Multiple Sclerosis isn't exactly a Southampton Clam Bake...
OneHundredPercent
not rated yet Aug 12, 2009
I agree with Tallison,there is no proof this will actually work on humans, seeing how its a human disease!
shavera
not rated yet Aug 12, 2009
to fixer et al, this disease, and others are kind of the fault of overactive immune systems. I may be mistaken, but the point of suppressing it isn't to make it completely non-functional, just to lower its response so it doesn't going around killing its own healthy cells.
djoseff
not rated yet Aug 12, 2009
To clarify, many diseases MS, SLE, RA, etc appear to be due to excessive or disordered immunity. Since no one knows how these are triggered, we presently can only try to suppress the problem. Thus far with current therapies, more than the disordered immunity is suppressed, so tightly focused treatment remains an elusive but hoped-for goal. Keep up the great work Dr. Galipeau!
otto1923
not rated yet Aug 18, 2009
You gentlepeoples have heard of using nature to treat autoimmune diseases?
http://en.wikiped..._therapy
-Restoring the symbiotes we evolved with (or less revolting facimiles)? Our overevolved immune systems are the inevitable result of overcrowding and living with our domesticated animals, which led to exposure to all manner of noxious infestation, and the bodys desperate attempts to compensate. Devolve the species by outsourcing the higher functions before it is too late!!