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75 EW GLAUCOMA July 2017 (nicotinamide mononucleotide adenylyltransferase 1), encoding an enzyme involved in the produc- tion of NAD+. Gene therapy alone, the study authors reported, was as effective at glaucoma prevention as administration of the lower dosage of nicotinamide. Drs. John and Wil- liams noted that a combination of this gene therapy as well as nicotin- amide was even more protective; it prevented glaucoma in 84% of eyes, which was up from about 70% for gene therapy or nicotinamide alone. "Gene therapy has already prov- en successful in clinical trials for rare Mendelian eye diseases. The benefit of gene therapy over taking nicotin- amide is that a single treatment may provide long-term—possibly life- long—protection," Drs. John and Williams said. "Based on previous gene-therapy studies in humans, and using the right agent of deliv- ery, one could expect that a single gene-therapy injection may protect for many years. Given that intravit- real injections are commonplace and that some patients have intravitreal injections once every 1 to 2 months (to treat AMD), we do not envision this being an obstacle for gene thera- py in glaucoma." Going forward, the team is forming partnerships for clinical trials of nicotinamide therapy in glaucoma patients. They are also considering this treatment in the context of other neurodegenerative diseases. "We will be delighted if nicotin- amide administration—and/or gene therapy—proves to provide effective therapeutic options for glaucoma," the researchers said. EW References 1. Williams PA, et al. Vitamin B3 modulates mi- tochondrial vulnerability and prevents glauco- ma in aged mice. Science. 2017;355:756–60. 2. Sauve AA. NAD+ and vitamin B3: From metabolism to therapies. J Pharmacol Exp Ther. 2008;324:883–93. 3. Li J, et al. A conserved NAD+ binding pock- et that regulates protein-protein interactions during aging. Science. 2017;355:1312–1217. Editors' note: Drs. John and Williams have no financial interests related to their comments. Contact information John: Sarah.Laskowski@jax.org Williams: Sarah.Laskowski@jax.org by Liz Hillman EyeWorld Staff Writer Vitamin B3 complex added to water helps prevent glaucoma the protective effect of this single vitamin against this mouse glauco- ma is surprising." While the researchers said they found the results in mice exciting and encouraging, human trials are still required to determine effica- cy and safety of a similar level in humans. Drs. John and Williams pointed out that nicotinamide is already a component of a regular diet and already has a strong safety profile, even at high doses. "Interested individuals should consider joining a trial and should certainly consult with their clini- cians before taking nicotinamide to ensure these high doses are appropriate for their situation and to avoid potential interactions with any other medications. It is im- portant to emphasize that we used nicotinamide versus other forms of vitamin B3, as different forms have different properties." In the mouse study, the nicotin- amide was mixed with drinking wa- ter or food, but for human patients, Drs. John and Williams said they envision taking it in tablet or other supplement form. Taking it a step further, the researchers also identified a gene- therapy application of NMNAT1 "Since NAD is a critical mol- ecule for many cellular reactions, including generation of the cellular energy supply, we reasoned that its lower levels due to age are likely to render retinal cells more vulnerable to stresses caused by high pressure inside the eye—intraocular pressure, IOP, another risk factor for glauco- ma," Drs. John and Williams said. Knowing that vitamin B3 is converted to NAD in the body, Drs. John and Williams and their fellow researchers administered it to mice genetically predisposed to develop glaucoma, hypothesizing that it could help reduce vulnerability to higher IOP associated with aging. According to Williams et al., "At the highest dose tested 93% of eyes did not develop glaucoma." "We were surprised at how potently it protected from an age-dependent, inherited glaucoma in mice," Drs. John and Williams said. "Our study shows that doses of nicotinamide can be directly neu- roprotective—protecting the retinal ganglion cells without lowering IOP. All currently approved glaucoma therapies lower IOP. Thus, nicotin- amide may provide an effective new class of neuroprotective glau- coma treatment. The magnitude of High doses of nicotinamide, the amide of vitamin B3, reduced incidence of glaucoma in genetically predisposed mice C ould preventing glaucoma be as simple as taking vita- min B3? Something close to that is what research- ers out of The Jackson Laboratory, Bar Harbor, Maine, are trying to find out after their recently published study found adding nico- tinamide (the amide of vitamin B3 complex) to water or food reduced development of the disease in genet- ically predisposed mice. 1 The team, led by Simon John, PhD, professor, The Jackson Lab- oratory, and investigator, Howard Hughes Medical Institute, Chevy Chase, Maryland, and the paper's first author Pete Williams, PhD, postdoctoral associate, The Jackson Laboratory, discovered that nicotin- amide adenine dinucleotide (NAD), increasingly recognized for its role in metabolic function and in the anti-aging process, decreases in the retina with increased age. 2,3 And it's well-understood that increased age is a major risk factor for glaucoma. Research highlight

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