Health knowledge made personal
Join this community!
› Share page:
Go
Search posts:

RESEARCHERS DISCOVER KEY TO STEM CELL THERAPY FOR MS PATIENTS

Posted Nov 09 2012 12:00am

  clinical trial capsules

We know stem cells work on MS, we just hadn’t figured out exactly how yet…and now we have!

- DG

CLEVELAND, Ohio One of the most promising and exciting treatment avenues for multiple sclerosis is the use of a patient’s own stem cells to try to stop or even repair some of the disease’s brain tissue damage.

But injecting a patient with a dose of his or her own bone-marrow stem cells was actually a pretty crude method of treating the disease, because no one was quite sure how or why it worked. Last year, doctors at the , University Hospitals Seidman Cancer Center and began trying this for MS patients in a after positive results were seen in mice.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheaths that surround and protect nerve cells. When myelin is damaged, the nerve cells are exposed and unable to do their job, which is sending signals to the brain and back. This results in the loss of motor skills, coordination and cognitive abilities.

Like many other researchers using stem cells, the local group didn’t know exactly how their treatment worked, but they knew that when they gave these human mesenchymal stem cells, or MSCs, to mice with a mouse version of the disease, the mice got better.

Figuring out why the mice improved could help researchers see if the MSC injection will work well in a particular patient before the patient is injected, and possibly augment or improve the treatment as well.

In May, the research group at CWRU, headed up by neurosciences professor Robert Miller , discovered exactly what it is in the stem-cell soup that has a healing effect: a large molecule called hepatocyte growth factor, or HGF. The team published their results in .

Miller’s group knew that it could be the stem cells themselves, by coming in physical contact with the myelin damage, that were having a healing effect. Or it could be something the stem cells secreted into the surrounding liquid culture, or media, they were grown in, that was key. HGF is secreted by the stem cells, Miller said.

The team identified the HGF by first injecting only the liquid the stem cells were grown in, but not the stem cells themselves, into the mice they were studying. The mice got better, so the team knew whatever was helping was in the media.

Next, they isolated the small, medium and large molecules from the media and tried each size on the mice. Only the large-molecule treatment had the healing effect, meaning that whatever was helping was somewhere in that mix, Miller said.

“The molecule that jumped out at us was HGF,” he said, because it is the right size, is made by MSCs, and in a couple of studies had been shown to be involved in myelin repair.

So the scientists took a purified sample of HGF and injected it into the sick mice. They got better. When they blocked the receptor for HGF in the mice, they stayed sick. It was pretty compelling evidence that they’d found what they’d been looking for, Miller said.

“We went on to show that HGF, like the MSCs, is regulating both the immune response, and it is independently promoting myelin repair in the brain,” he said.

MSCs, taken from the bone marrow, are currently being tested in more than 150 clinical trials in the and around the world to treat conditions such as osteoarthritis, diabetes, emphysema and stroke.

The local Phase 1 trial has enrolled 16 of 24 total patients, and eight of them have completed the trial protocol, said Dr. Jeffrey Cohen , Cleveland Clinic neurologist and lead investigator of the trial.

So far, the treatment seems to be working, Cohen said.

“It’s a little early to be saying it, but things have looked encouraging.”

And there have been no safety concerns and almost no side effects. There has also been no activation an aggravation or return of symptoms of this relapsing disease in the patients involved, which has happened unexpectedly with other types of MS treatments.

Miller’s discovery won’t change the course of the trial currently under way at the Clinic and UH, but it may change the future of MSC treatment.

While they don’t know yet what the outcome of that trial will be, it’s possible that if a patient doesn’t respond to the treatment, it could mean that his stem cells aren’t producing enough HGF to be effective at healing, Miller said. Miller will be studying MSC samples from all the patients in the trial to find out if those who are better at producing HGF fare better.

He’ll also be trying to see if they can predict how well a patient will do based on his HGF levels in the MSC sample.

“Finally, though we’re a long way from this, maybe we could augment the expression of HGF in patients whose stem cells aren’t that effective to enhance their effectiveness,” he said.

But why not just inject the HGF alone? Miller said there are two reasons. First, the receptor for HGF in the cells, called c-MET, has been implicated in liver and breast cancer. Injecting HGF by itself into the body may stimulate the c-MET pathway, he said, and the research team is not willing to risk that.

“The stem cells have the advantage that they tend to home to the area of insult, so they don’t stick around in other parts of the body,” he said. “They target the treatment where it’s needed.”

Miller said his group is experimenting with a way of delivering HGF directly into the area of injury in the brain to minimize its contact with the rest of the body. HGF and c-MET are not associated with brain tumors.

They are also trying to test small fragments of the growth factor as a treatment, to see if they can eliminate some of the cancer concerns.

Cohen’s group hopes to have results from the Phase 1 trial available in the spring and has already started planning a larger study based on those results.

Post a comment
Write a comment:

Related Searches