HSCT shows signs of restoring nerves

Discuss stem cells, adult and embryonic, and their therapeutic potential for MS here.

HSCT shows signs of restoring nerves

Postby TwistedHelix » Wed May 21, 2008 7:37 am

I think this is the same Canadian team that Bromley has been posting about, but with an emphasis on repair that I haven't seen before, (I've probably just missed it). The fact that improvement has taken two years to show somehow makes it seem more credible: a friend of mine had a nerve transplant in his arm which took two years to connect – and that, of course, was his peripheral nervous system – professor Scolding's trial in Bristol is also expected to take time to show results. Maybe there won't be any need for the aggressive chemotherapy after all:

Bone marrow treatments restore nerves in multiple sclerosis patients
An experiment that went wrong may provide a new way to treat multiple sclerosis, a Canadian researcher said on Tuesday.

Patients who got bone marrow stem-cell transplants -- similar to those given to leukemia patients -- have enjoyed a mysterious remission of their disease.

And Dr. Mark Freedman of the University of Ottawa is not sure why.

"Not a single patient, and it's almost seven years, has ever had a relapse," Freedman said.

Multiple sclerosis or MS affects an estimated 1 million people globally. There is no cure.

It can cause mild illness in some people while causing permanent disability in others. Symptoms may include numbness or weakness in one or more limbs, partial or complete loss of vision, and an unsteady gait.

Freedman, who specializes in treating MS, wanted to study how the disease unfolds. He set up an experiment in which doctors destroyed the bone marrow and thus the immune systems of MS patients.

Then stem cells known as hematopoeitic stem cells, blood-forming cells taken from the bone marrow, were transplanted back into the patients.

"We weren't looking for improvement," Freedman told a stem cell seminar at the U.S. National Institutes of Health.

"The actual study was to reboot the immune system."

Once MS is diagnosed, Freedman said, "you've already missed the boat. We figured we would reboot the immune system and watch the disease evolve. It failed."

STEM CELL REPAIR

They had thought that destroying the bone marrow would improve symptoms within a year. After all, MS is believed to be an autoimmune disease, in which immune system cells mistakenly attack the fatty myelin sheath that protects nerve strands.

Patients lose the ability to move as the thin strands that connect one nerve cell to another wither.

Instead, improvements began two years after treatment.

Freedman reported to the seminar about 17 of the patients he has given the transplants to.

"We have yet to get the disease to restart," he said. Patients are not developing some of the characteristic brain lesions seen in MS. "But we are seeing this repair."

MS patients often have hard-to-predict changes in their symptoms and disease course, so Freedman says his team must study the patients longer before they can say precisely what is going on.

"We are trying to find out what is happening and what could possibly be the source of repair," Freedman said.

But he has found some hints that may help doctors who treat MS by using drugs to suppress the immune system.

"Those with a lot of inflammation going on were the most likely to benefit (from the treatment)," he said.

"We need some degree of inflammation." While inflammation may be the process that destroys myelin, it could be that the body needs some inflammation to make repairs, Freedman said.

Immune cells secrete compounds known as cytokines. While these are linked with inflammation, they may also direct cells, perhaps even the stem cells, to regenerate.

The treatment itself is dangerous -- one patient died when the chemicals used to destroy his bone marrow also badly damaged his liver.

Source: Reuters Canada © Thomson Reuters 2008 (07/05/08)
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Postby mrhodes40 » Wed May 21, 2008 8:24 am

Thanks for posting this! IT is great!

I have been thinking about the revimmune idea, kind of the same without the radiation to kill the marrow itself, but here is what I have been wondering.

One of the things done in these kinds of treatments is people are given neupogen to cause the bone marrow to make a whole bunch of stem cells.

In the ASCT study mentioned above it would ahve been given to people before the treatment so they could "harvest" stem cells ahead of time to do the reimplantaion after they killed the marrow with chemo and radiation.

In the revimmune model, neupogen is given after the cyclophosphamide to restart the marrow (which has been seletively spared by this form of treatment).

What I have been wondering is if in fact neupogen would be a stem cell treatment all on its own. Forget clinics in Mexico for thousands of dollars!

Why not? give the neupogen and let the body make its own. The question in MS would be is the disease process itself going to harm the new cells and thus make it moot anyway.

Related to the mention above that stems repair, Tulane university and an MD called Prockop has been working on a stem cell transplant procedure and he was interviewed on my local radio station.

He said in their work on mice with a natural diabetes they gave the mice human stem cells and then looked at the mice to see if they made human insulin.

They did, but they ALSO made mouse insulin, which shocked them. The stems had healed the normal diabetes for the mouse. Furthermore it healed the mouses kidneys which were damaged by the diabetes. They said the real beauty of stems is not that they regenerate stuff but that they bring all kinds of beneficial cytokines and healing to any area that needs it.

I too have thought that the idea of allowing some level of inflammation would benefit the healing process, and I have wondered if the broad antiinflammatory approaches that kill off all possible inflammation might with time show a poorer outcome, but like this study,I have thought it would take a long time to show that.

Interesting post!
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Postby TwistedHelix » Thu May 22, 2008 6:17 am

Hi Marie,
I really like the idea that neupogen could be enough on its own. I agree that the MS process may stop the new cells working, but on the other hand it might just be that flooding the system with new cells could overwhelm, (or at least overtake), MS in exactly the same way as MS normally overwhelms the body's slow attempts at repair… it's a nice thought!
Stem cells are full of surprises, as those diabetic mice have shown, I think that given the right environment – and more time to take effect – they're going to amaze us.
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Postby mrhodes40 » Thu May 22, 2008 6:39 am

Yeah, it's interesting isn't it?

I am very hopeful about these kinds of approaches.
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Postby CureOrBust » Fri May 23, 2008 6:43 pm

I am really hopeful for something along these lines, but I question whether the neupogen's effects will cause the stem cells in the marrow to migrate to other areas (ie the brain)? and hence why the scientists are probably not trying the same.
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Postby mrhodes40 » Sun May 25, 2008 3:51 pm

Actually many studies are showing that stems given in an IV peripherally--not injected into the brain or anything--will go where the damage is.

This paper is talking about the researchers colonizing the marrow with human type stems then inducing damage to see what happened, and it went from the marrow to the damaged liver.

http://www.futurepundit.com/archives/001257.html

This one shows tht if injected into the ventricles, the cells migrate widely

http://www.sciencedaily.com/releases/19 ... 073135.htm

the best one is below....
http://www.sciencedaily.com/releases/20 ... 071615.htm
By 4 months after the transplants, they found a significant number of neuronal cells in several brain regions, including the cortex, the hypothalamus, and the striatum, that were descendants of the transplanted cells. This suggests that stem cells from elsewhere in the body can enter the brain and differentiate into neuronal cells, says Dr. Mezey.

Not far fetched, reality I hope soon. NO reason at all to thikn that neupogen which stimulates the bone marrow to make stems would not result in them migrating to the brain.

In fact the thing that got me noticing about the neupogen was theat the resarcher in the first paper at the top of this thread mentioned that maybe the stems were the cause of the two years later improvement.

I am going to guess that someone tries it before too long.

Crumb maybe an adventurous person could contact a hematologist who would do it for a person "off label" and out of pocket.
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