• 19:00 03 November 2005
• NewScientist.com news service
• Gaia Vince

A new pathway for treating multiple sclerosis may have been found, if “exciting” results in mice can be replicated in humans.

MS is an incurable degenerative disease caused by the body’s immune system attacking the protective myelin sheath encasing the nerves that make up the central nervous system. The nerve fibres become increasingly damaged by scar tissue, known as sclerosis, which leads to paralysis and loss of speech and vision.

But researchers trying a novel therapy on a mouse version of MS report that the mice showed “almost no inflammation of the myelin sheath and no nerve damage”. Furthermore, MS is characterised by periods of remission and relapse, but the mice recovered with fewer and far less severe relapses.

The therapy targets immune system cells called T-cells. These malfunction in MS patients, producing inflammatory molecules that destroy the myelin sheath. The new treatment, which uses a class of molecules called kynurenines, works by inhibiting the T-cells’ production of inflammatory molecules and prompting them to produce agents that “mop up” the molecules.

Suppressed and slowed

The work began with Larry Steinman at Stanford School of Medicine in California, US, and Michael Platten at the University of Tubingen in Germany, and colleagues. First, they selected a break-down product – a kynurenine – of a naturally occurring amino acid called tryptophan. Tryptophan is a constituent of most proteins and is known to play an important role in immunity.

The group then induced an MS-type illness called experimental autoimmune encephalomyelitis in 24 mice. On the occasion of their first relapse half were given a daily dose of a synthetic version of the kynurenine for 49 days.

“All the mice went into remission, but the mice on the tablets stayed healthy for much longer," says Platten. "The relapses were far less severe and they did not have a return of the paralysis. The drug actually suppressed the disease and slowed its progression.”

The mice on the tablets also had “re-programmed” T-cell function, he adds: “Instead of being pro-inflammatory, the T-cells became anti-inflammatory, helping to heal the myelin sheath and suppressing paralysis.”

Dearth of new ideas

Examination of the mice at the end of the experiment showed that the treated mice had undamaged nerve cells and no spread of the condition to the brain, whereas this had occurred in the untreated control group. There were no apparent side effects from the treatment.

“And, when we gave a blood transfusion from mice who had received the treatment to other sick mice, the transferred T-cells retained their ability to suppress the disease,” adds Steinman, suggesting that the therapy may only need to be administered for a short period.

Peter Brophy, an MS expert at the University of Edinburgh in the UK, says the research is very exciting, providing an “interesting new pathway after a dearth of new ideas for MS treatments".

"It’s completely different to any of the treatments around at the moment, and the study shows a really striking effect on T-cell behaviour,” he says. “The fact that it can be given orally rather than by injection [like all current treatments] also makes it attractive.”

Safety tested

But Brophy cautions that the mouse model of MS, while the best animal model available, does show differences to the human disease and drugs that have worked on mice in the past, have not had the same success in humans.

Another advantage kynurenine has over other candidate treatments is that it is has already proved its safety. Not only is it a derivative of an amino acid that occurs naturally in the human body, but it has passed phase I clinical trials in Japan as a potential treatment for allergy sufferers.

“I expect we will be able to proceed directly to phase II clinical trials in patients in 2006 and start helping people with MS,” Steinman says.

Journal reference: Science (vol 310, p850)

http://www.newscientist.com/article.ns?id=dn8263