A small trial at a US hospital where patients with early stage MS had their own immune system stem cells transplanted back into their bodies appears to have reversed the neurological dysfunction of the early stages of the disease by causing their immune systems to "reset". The scientists said the results should now be confirmed with a larger, randomized trial.

The trial was the work of researchers from Northwestern University's Feinberg School of Medicine in Chicago, plus colleagues from other research centres in and outside the US, and is published early online in The Lancet Neurology on 30 January; it will appear in the March print issue.

The patients on the small phase I/II trial experienced improvements in several areas affected by their MS, including walking, ataxia (loss of muscle coordination), limb strength, vision, and incontinence. They continued to improve for 24 months after receiving the transplants and then stabilized.

MS (Multiple Sclerosis) is an autoimmune disease where the person's own immune system attacks their central nervous system causing all kinds of neurological dysfunction such as loss of control over muscles and loss of ability to take in information through the senses.

The early stage is called relapsing-remitting MS and the person has intermittent symptoms from which they partially or fully recover and then relapse into again. These include visual impairment, fatigue, sensory problems, limb weakness or paralysis, tremors, lack of coordination, problems with balance, changes in bowel and bladder, and psychological changes.

After about 10 to 15 years of relapsing-remitting MS, patients enter another stage called secondary progressive MS, where symptoms steadily become worse and irreversible.

Lead researcher on the team, Dr Richard Burt, who works at using immunotherapy for autoimmune diseases at the Feinberg School said:

"This is the first time we have turned the tide on this disease."

For the trial, Burt and colleagues recruited 21 patients aged 20 to 53 who had had MS for an average of 5 years. They all had relapsing-remitting multiple sclerosis that had been treated with interferon beta for at least 6 months but with no response.

First, they had to destroy the patients' immune system with chemotherapy, then they injected them with their own stem cells that had been harvested before the chemo. This seeded a new immune system. The procedure is called "autologous non-myeloablative haematopoietic stem-cell transplantion".

After an average follow-up of three years after receiving their transplants (which took place between January 2003 and February 2005), 17 patients (81 per cent) improved by at least one point on a disability scale. And for all patients, the disease had stopped progressing. Five patients relapsed in the early days, but then experienced remission after further immunosuppression.

Burt said that they focused on destroying only the immune system part of the bone marrow and then regenerating it, a procedure that is less toxic than traditional chemotherapy for cancer.

But amazingly, when the new immune system is created, the patient's new white blood cells are self-tolerant, as Burt explained:

"In MS the immune system is attacking your brain."

"After the procedure, it doesn't do that anymore," he said.

The authors concluded from the trial that this type of stem cell transplantation in patients with relapsing-remitting MS "reverses neurological deficits", and Burt said the results were "promising and exciting", but to get real proof, you need a randomized trial, which he has already launched.

Burt has been working with MS patients for some time; in earlier research he tried transplanting immune system cells into patients with late-stage MS but it didn't help them like it did the early stage patients in this trial.

"Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study."
Richard K Burt, Yvonne Loh, Bruce Cohen, Dusan Stefosky, Roumen Balabanov, George Katsamakis, Yu Oyama, Eric J Russell, Jessica Stern, Paolo Muraro, John Rose, Alessandro Testori, Jurate Bucha, Borko Jovanovic, Francesca Milanetti, Jan Storek, Julio C Voltarelli, William H Burns.
The Lancet Neurology published online ahead of print 30 January 2009.
doi:10.1016/S1474-4422(09)70017-1

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Sources: Journal Abstract, Northwestern University press release via ScienceDaily.

Written by: Catharine Paddock, PhD