Increasing levels of nicotinamide adenine dinucleotide (NAD) in the nervous system by administering NAD’s chemical precursor, nicotinamide—a form of vitamin B3—may protect people with multiple sclerosis (MS) from severe long-term disability. Using a mouse model of MS, researchers in the Neurobiology Program at Children’s Hospital Boston found strong evidence that nicotinamide may protect against neuronal damage in the chronic progressive phase of MS. Their findings appear in the September 20 issue of the Journal of Neuroscience.

A team led by Shinjiro Kaneko, MD, a research fellow at Children’s Hospital, and senior investigator Zhigang He, PhD, worked with mice that had experimental autoimmune encephalitis (EAE). They found that nicotinamide protected the animals’ axons from degeneration—not only preventing axon inflammation and myelin loss but also preventing further degradation of axons that had already lost their myelin.

Mice with EAE that received daily subcutaneous nicotinamide injections had a delayed onset of neurologic disability, and the severity of their deficits was reduced for at least eight weeks after treatment, the investigators reported. On a scale of 1 to 5 (with 1 indicating mild weakness only in the tail; 4, paralysis involving all four limbs; and 5, death from the disease), mice receiving the highest doses of nicotinamide had neurologic scores between 1 and 2, while control mice had scores between 3 and 4.

The team also demonstrated that nicotinamide works by decreasing NAD levels in the spinal cord, that NAD levels decrease when axons degenerate, and that giving NAD directly also prevented axon degeneration. "The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage," said Dr. Kaneko. "In the early phase of MS, anti-inflammatory drugs may work, but long term, you need to protect against axonal damage."

NR