The trial—the first of its kind in the United States—is thework of a consortium of researchers from the Cleveland Clinic, UniversityHospitals' Seidman Cancer Center and Case Western Reserve University (CWRU).Researchers are harvesting mesenchymal stem cells (MSCs)—or adult stem cellsfound in the bone marrow—of patients with MS, cultivated them in a CWRU lab andthen injecting them intravenously back onto the patients.
The primary goal of these efforts is to test the safety andfeasibility of using the body's own stem cells to treat MS. More long-term,though, the researchers hope to find evidence that these transplanted cells canhelp moderate the overactive immune systems of MS patients—or to developregenerative strategies to repair or even stop the debilitation seen in themore progressive stages of the disease.
The researchers are interested in MSCs because they haveseveral properties that could possibly make them helpful in treating MS, saysDr. Jeffrey Cohen, lead investigator of the trial.
"One reason is that they have the ability, in a number ofanimal models of other human diseases, to increase repair in tissue damages—notjust by replacing the cells themselves, but also by creating an environmentthat supports normal repair mechanisms that are already present in tissue,"says Cohen, who in addition to seeing patients in a clinical setting, directsthe Experimental Therapeutics Program at the Cleveland Clinic's Mellen Centerfor Multiple Sclerosis Treatment. "In addition, the anti-inflammatory effectsof these cells are quite potent in modulating a number of immune mechanisms,may of which have been implicated in MS. Finally, these cells appear to havethe ability to migrate through the blood into tissues that are inflamed andseek out areas of damage. This is much more convenient than directly injectingthem into the brain."
The study is the clinic's first foray into performing stemcell research on MS patients, Cohen says. The researchers have enrolled fourpatients in Phase I studies so far. After a formal safety review, they hope toenroll a total of 24 patients by the end of 2012.
Getting the trial off the ground hasn't been easy.Researchers first had conversations about it in early 2007, but had to workearnestly for a few years to obtain funding.
"This study is fully funded by grants, rather thanindustry," Cohen notes.
But the researchers' main stumbling block, he says, wasobtaining the necessary regulatory approval to proceed.
"Even though there has been some experience with using thesecells in other disease areas, the overall published experience has been verymodest," Cohen explains. "We hope to get the reassurance we need to move at amore rapid place."
The researchers have not yet considered a commercial partnerto bring the results of their findings to market, he notes. Instead, they arefocused more on furthering the science involved in using MSCs.
"We're less encumbered by commercial constraints, and moreconcerned with how a treatment would be offered more broadly down the road," hesays. "Even if the cells are not commercializable, the data we are generatingwill surely help other people who have commercial plans underway."
The outcome of this trial is expected to be a significantadvance in the field of MS research. About 10,000 people in the United Statesare diagnosed with MS every year, and the disease primarily affects women.There is no known cure. Cohen notes that medications currently approved for thetreatment of MS focus on preventing disease activity, but do not addressdamage. They can also have adverse effects or be poorly tolerated.
"There is a huge unmet need for therapies for MS patients,"Cohen says.
MSCs have also been tested on and demonstrated potential inseveral other conditions such as heart disease, stroke, spinal cord injury andnon-healing bone fractures, he adds.
"MSC transplantation is a very effective treatment forconditions where anti-inflammatory actions are discovered," Cohen says. "It'sbeing evaluated in a wide variety of conditions. The areas that have receivedthe most attention are cancer, graft-versus-host disease, bone marrowtransplants, coronary disease and peripheral vascular disease. There are also anumber of smaller studies in diseases like irritable bowel syndrome. But theoverall experience there is relatively modest."
