Nature News 干细胞治疗可能逆转多发性硬化症状
MS stem-cell trial shows promise - Multiple sclerosis treatment seems to reverse symptoms.
Bone marrow stem cells may have helped patients with multiple sclerosis.
A stem-cell therapy appears to help some patients with early-stage multiple sclerosis recover, according to results from a preliminary study.
Multiple sclerosis (MS) is a chronic disease where the body's immune system attacks the central nervous system. White blood cells in the body attack the protective myelin sheaths surrounding nerve fibres in the brain and spinal cord. Although symptoms of the disease wax and wane, they generally grow worse over time and include fatigue, blurred vision and difficulty walking.
In the new trial, the patients' immune cells were first destroyed and they were then injected with blood stem cells taken from their bone marrow. Seventeen of the 21 patients treated in his study improved, suffering fewer problems with their balance or vision, and none declined over the 2-4 years they took part in the study.
This marks the first time a technique "has actually shown reversal" of neurologic loss caused by this disease, says Richard Burt of Northwestern University in Chicago, who led the study.
Normally, when MS drugs fail to calm the immune system, doctors may adapt a strategy currently used for blood cancers: a combination of toxins and radiation to destroy the bone marrow â??which contains the patient's blood-forming system â??followed by a transplant of healthy cells to restore it.
Though such techniques can be effective, they carry the risk of serious side-effects and death.
The current work uses less toxic drugs to primarily kill one type of immune cell â??the white blood cells known as T-cells. Burt and colleagues were also able to administer the stem cells at earlier stages of MS, when the brain is more capable of repairing damage.
Edwin McClure, a 24-year-old advertising student at Virginia Commonwealth University, was one of the patients treated. He says his neurologist referred him to the study after he'd tried "three different drugs over three years that were all pretty much ineffective". Before the study, he says, he had to give himself a shot every other day; nonetheless, fatigue, poor balance and dimmed vision limited his activities. Now, McClure says, he no longer has those problems or takes medications for MS.
A lot of research suggests that the early "relapsing-remitting" stage of MS is the most treatable, says Patricia O'Looney, vice president for biomedical research at the National Multiple Sclerosis Society in New York. This is when the inflammation that destroys myelin sheaths is at its peak.
"To try to stop progression and loss of tissue, you have to try to get that inflammation under control," she says. Safer, earlier ways of destroying and replacing the immune system might do that, she says, but, she still recommends caution about the transplantation technique. "It's not an easy procedure," she says. "Although they are impressive results, it's a preliminary study."
Burt's therapy is probably less toxic than other forms of intense immunosuppression, says Gianluigi Mancardi of University of Genova in Italy, who wrote a commentary accompanying the study2. But, he says, "Burt's therapy cannot be considered gentle, because there are certainly side-effects of some importance".
Burt believes that the risk of death from this procedure is less than 1%. In comparison, the MS drug Tysabri (natalizumab), a monoclonal antibody, has about a 1 in 1000 chance of causing a serious viral infection, but those risks were considered so serious that it was initially withdrawn from sale by the manufacturer. It is now only prescribed under a special prescription programme in the United States and carries serious warnings in Europe.
Walter Royal, director of the Maryland Center for Multiple Sclerosis at the University of Maryland, Baltimore, highlights some of the study's strengths. He notes the researchers tried to control for the wide fluctuations often observed in MS, by recruiting patients only after their condition stabilized following a relapse. The patients were also monitored over an average of three years, he says, "which certainly was long enough to know if improvement was transient". Nonetheless, larger studies in multiple centres are now needed, particularly to assess risks, Royal adds.
Burt agrees that his team's study is small and lacked a control or comparison group. He is currently recruiting patients for a larger, randomized trial. Even if further work shows that the treatment is effective for the early stage of the disease, the technique does not help patients with later "progressive" MS, says Burt. Though bone marrow stem cells reboot the immune system, they cannot repair myelin after axons have been very badly damaged.