To find out if the balance of NAD+ and NADH was critical for tumor cell behavior, the team proceeded to insert a yeast gene into cancer cells that caused a shift toward more NAD+. To the scientists' amazement, this shift caused the tumor cells to become less aggressive.
"It was a really happy moment for me," said Santidrian. But the more exciting moments, he said, were yet to come.
To confirm and extend the initial findings, the team altered genes tied to NAD+ production. The resulting shift again showed that higher NADH levels meant more aggressive tumors, while increased NAD+ had the opposite effect.
The next logical step was to find a simple way to enhance the critical NAD+ level therapeutically. So the team explored what would happen if mice with breast cancer were fed water spiked with nicotinamide, a precursor for NAD+ production. The scientists found cancer development was dramatically slowed down, and the mice lived longer
"In animal models at various stages, we see that we can actually prevent progression of the disease," said Felding.
Now the group is working toward human trials to learn whether nicotinamide or other NAD+ precursors will have similarly impressive results in humans. Since NAD+ precursors are already used for other purposes, such as controlling cholesterol levels, achieving approval for human clinical trials should be simpler than is normally the case.
"It is not a totally new treatment that would need to be tested for toxicity and side effects like a new drug," said Felding. "And we already know the precursors can be easily ingested."
If manipulating the NAD+/NADH ratio in humans has the same effect as in mice, the results could be profound. Such treatment could benefit people at risk of developing aggressive breast cancer, offer complimentary treatment to chemo and radiation therapy to avoid disease recurrence, and maybe even p
|Contact: Mika Ono|
Scripps Research Institute