New Vitamin May Relieve a Painful Problem

One of the long-term side effects of receiving high doses of anticancer drugs can be peripheral neuropathy, often experienced as pain and numbness in the hands and feet.

Focus article photo

Charles Brenner, PhD, discovered a new vitamin that could protect against peripheral neuropathy.

The National Institutes of Health describes it "like static on a telephone line," disrupting communication between the brain and spinal cord with other parts of the body. "Cancer chemotherapy agents are intended to target tumors," explains Charles Brenner, PhD, associate director of basic science, at Norris Cotton Cancer Center, "but the collateral damage of chemotherapy can damage neurons, particularly in the peripheral nervous system."

According to Ellen Lavoie Smith, PhD, ARNP, director of the Cancer Survivor Program and a specialist in peripheral neuropathy, there currently is no good treatment to prevent or treat the condition. "There are things that have been used, but nothing is a home run right now," she says. But during the rigorous tying up of loose ends of a scientific experiment, Brenner's lab discovered a molecule that may provide a pathway to treatment.

At the center of Brenner's work is a vitamin he discovered, called NR (nicotinamide riboside), which is found naturally in milk. NR is used for the synthesis of NAD (nicotinamide adenine dinucleotide), a compound fundamental to the production of energy in all living systems. Brenner found that giving yeast cells NR increases NAD synthesis, which boosts activity of an enzyme called Sir2 and extends the lifespan of yeast cells. The benefits are not confined to yeast. In mice, NR also protects particular neurons from damage. "If you give peripheral neurons NR, you can protect them from conditions that cause degeneration," explains Brenner. However, the cellular mechanism by which NR works is not understood entirely. It's not known, for example, if Sir2 is the real key to protecting neurons.

With the help of funds generated by the Prouty, Brenner, a geneticist and biochemist, has begun preliminary work with clinical pharmacologist Lionel Lewis, MB, MD, synthetic chemist Alex Pletnev, PhD, and surgeon Jack Hoopes, DVM, on a dosage study to determine how much NR is required to create a protective effect. "We'd like to translate our basic science discoveries into a first of its type agent that would protect patients with cancer from the neurotoxic effects of chemotherapy," explains Brenner. A pill to protect against nerve damage is a long ways off, but such a drug might also be able to protect against development of other neurodegenerative diseases. Until then, Brenner and his colleagues continue to unlock the mysteries of how cells work. "That's basically what we try to do every day," he says.

April 20, 2008