Science Editor

In the Jan. 30, 2009, online edition of Lancet Neurology, doctors reported that when they transplanted autologous stem cells into patients with early-stage multiple sclerosis, roughly 80 percent of the patients improved neurologically by at least 1 point on the so-called EDSS scale, which measures neurological disability.

During follow-up that lasted for an average of three years, none of the patients progressed to late-stage multiple sclerosis.

"All drugs currently approved have been approved on the basis of their ability to slow the progression" of multiple sclerosis, first author Richard Burt told BioWorld Today. But through the transplantation procedure, "we reversed neurological disability."

Why the immune system sometimes turns on itself in multiple sclerosis - or any other autoimmune disease, for that matter - is still unknown. But once they have gone bad, "these cells can be around for many decades," Burt said.

In their Phase I/II trial, the researchers removed blood stem cells from the patients before selectively killing off the immune system component of their bone marrow via chemotherapy, and re-introduced the stem cells. The procedure, Burt said, "allows the stem cells to make new, but better, immune cells" that no longer attack the myelin sheath.

Burt and his colleagues, as well as other groups, had tried to use transplantation, but those attempts have been unsuccessful, quite possibly because those groups treated late-stage patients.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the neuronal myelin sheath, which insulates nerve cells and makes signal conduction possible.

The disease is at first intermittent, or so-called relapsing remitting MS. Patients have flareups, but symptoms lessen or even disappear in between acute episodes. Most patients, however, ultimately progress to so-called secondary progressive multiple sclerosis, which is characterized by a steady worsening of irreversible symptoms.

Symptoms in early stage MS are caused by inflammation and reduced neural conduction - nerve cells are still there but temporarily less able to transmit signals as their myelin sheath is attacked. In late-stage multiple sclerosis, the problems are caused by actual neural degeneration. That is, the damage to their insulation initially snarls transmission, but ultimately causes the cells themselves to throw in the towel. The new results suggested that stem cell transplantation might be useful for patients whose disease has not yet progressed to the neurodegenerative stage.

Burt warned that "we need to prove [the procedure's benefits] in a randomized trial." That was echoed by a statement put out by the British multiple sclerosis society, which called the work "very encouraging" but also noted that some of the patients received Genzyme Corp's alemtuzumab (Campath), an antibody that has been approved for CLL, but is also in Phase III trials for MS and has been "shown to halt and potentially reverse disability." The MS society concluded that "positive results may not be solely from the use of stem cells."

A randomized controlled trial that will, among other things, tease out the relative contributions of stem cells and alemtuzumab has begun and currently is enrolling patients, though Burt refused to estimate when data from the trial might be forthcoming, saying only that "everything always takes longer than I think."

In the meantime, his group continues to follow the patients in the trial now published in Lancet Neurology, and he is encouraged by the continued progress that some of them continue to make.

He said that at five-years post-transplant, there is one patient who is neurologically normal.