Cleveland researchers find key to stem-cell therapy for MS patients: Discoveries
Published: Tuesday, September 04, 2012, 7:21 AM Updated: Tuesday, September 04, 2012, 2:02 PM
CLEVELAND, Ohio — …Figuring out why the mice improved could help researchers see if the MSC injection will work well in a particular patientbefore the patient is injected, and possibly augment or improve the treatment as well.
In May, the research group atCWRU, 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 Nature Neuroscience.
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 ofstudies 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 United States 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 hisstem 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 hisHGF 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.”