A study published in Science shows that high doses of vitamin B3 may prevent development of glaucoma and other neurodegenerative conditions and slow progression in those already diagnosed.
Mice genetically predisposed to glaucoma averted any sign of early disease after drinking water supplemented with nicotinamide, an amide form of B3 (also known as niacinamide) that converts inside the body to the enzyme nicotinamide adenine dinucleotide (NAD+). When given to older mice that already displayed signs of glaucoma, the vitamin halted further progression. Overall, 93% of mice did not develop glaucoma when given the highest tested dose.
Previous discoveries have established that retinal levels of NAD+, an enzyme essential for mitochondrial respiration and other redox reactions, are reduced with age. The depletion of NAD+ weakens the metabolism of ganglion cells and inhibits their ability to defend against glaucomatous damage.
The team then tested whether similar results could be obtained by introducing the gene that encodes the enzyme organisms use to create NAD+ from dietary nicotinamide into the mutant mice. Just one application of Nmnat1 gene therapy prevented the development of glaucoma.
Research leader Simon W.M. John, PhD, is now pursuing clinical partnerships to evaluate the effectiveness of B3 as a preventative and interventional agent against glaucoma in humans. The promise of an efficient, single treatment is especially appealing considering the high treatment burden of current glaucoma therapies.
“It can be a problem for patients, especially the elderly, to take their drugs every day and in the correct dose,” said first author Pete Williams, PhD. “So gene therapy could be a one-shot, protective treatment.”
The protective role of NAD+ in optic nerve health may also be applicable to other neurodegenerative conditions.
“We wanted to identify key age-related susceptibility factors that change with age in the eye,” John says, “and that therefore increase vulnerability to disease and in particular neuronal disease.”