B Vitamin Prevents MS Disability in Mice

BOSTON, Sept. 20 -- A form of niacin may be a novel treatment for chronic progressive multiple sclerosis, according to researchers here.

In a mouse model of MS, nicotinamide - the amide form of niacin, or vitamin B3 - significantly prevented neurological disability, said Shinjiro Kaneko, M.D., of Children's Hospital Boston.

The finding, reported in the Sept. 20 issue of Journal of Neuroscience, raises the possibility that the vitamin "may be a promising candidate as a neuroprotective treatment for MS patients," said Dr. Kaneko and colleagues.

While the work is still preclinical, "we hope that our work will initiate a clinical trial, and that nicotinamide could be used in real patients," Dr. Kaneko said.

Available treatments for MS are primarily anti-inflammatory, and are only effective during the relapsing-remitting phase of the disease, the researchers noted. In chronic progressive MS, no therapy is known.

There is evidence that damage to axons is closely correlated with the neurological damage of MS seen in the progressive phase, Dr. Kaneko and colleagues observed, and that damage is similar in some respects to "Wallerian degeneration" seen in injured nerve tissue.

Also, in mutant mice that overexpress a fusion protein that is required for biosynthesis of nicotinamide adenine dinucleotide, Wallerian degeneration is markedly slowed, the researchers noted.

In a series of experiments, they showed that the mutant mice also had a reduction of neurological disability when researchers induced experimental autoimmune encephalomyelitis, the animal model for MS.

The implication is that similar mechanisms - mainly axonal damage -- are involved in the neurological disability that characterizes both Wallerian degeneration and experimental autoimmune encephalomyelitis.

Connecting the dots, Dr. Kaneko and colleagues noted that NAm is the chemical precursor of nicotinamide adenine dinucleotide, so that injections of nicotinamide might increase the biological levels of nicotinamide adenine dinucleotide and possibly prevent neuronal damage and subsequent disability in experimental autoimmune encephalomyelitis.

When wild-type and mutant mice were injected with nicotinamide at the same time as the experimenters began inducing experimental autoimmune encephalomyelitis, the onset of disease was significantly slowed, compared to control mice, and the severity of symptoms was reduced.

Strikingly, however, the same effect was seen in established disease.

The researchers gave daily injections of nicotinamide to wild-type mice (at 500 mg/kg of body weight) starting 10 days after they had induced experimental autoimmune encephalomyelitis, when most of the animals were already displaying signs of neurological disability, such as hindlimb weakness or paralysis.

The researchers found:

• The treated mice had significantly lower disability scores starting at day 13 (at P<0.01) and little or no progression, compared to control animals.
• At both two and four weeks after the disease was induced, nicotinamide adenine dinucleotide levels in the treated mice were significantly higher than those in control animals, at P<0.05 and P<0.001 respectively.

Nicotinamide has several characteristics that make it a promising therapeutic agent, Dr. Kaneko and colleagues said: it readily crosses the blood-brain barrier, is inexpensive and available in any drugstore, and its close relative, vitamin B3, is already used clinically to treat pellagra, high cholesterol, and other disorders.

However, the doses used in the mice would translate in humans to much higher levels than are usually used clinically, Dr. Kaneko cautioned.

The study was financed by National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke.