Oral Supplements May Promote Neurorecovery

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Could ophthalmologists eventually be able to protect glaucoma pa­tients’ vision by giving them nutritional supplements that rev up the mitochon­dria in retinal ganglion cells (RGCs)? Results of a small phase 2 dosing and safety trial suggest that the answer might be yes.¹

“This our first attempt at proof-of-concept in humans for this type of intervention in glaucoma,” said study leader Jeffrey M. Liebmann, MD, at Columbia University Medical Center in New York City. “So far, it looks like there’s a potential role for vitamin and nutritional supplementation as a treat­ment to help protect nerve cells.”

With this neurorecovery strategy, “you postulate that some RGCs are sick—and that if you provide them with neuroenhancing compounds, the cells will function a little bit better, and we’ll see a small uptick in visual function,” Dr. Liebmann added.

RGC LOSS. RGCs are plentiful in a healthy mouse (top). In comparison, the mouse with glaucoma (bottom) has experienced substantial RGC loss.

Two compounds tested together. In the study, 32 participants with treat­ed open-angle glaucoma and moderate visual field loss were randomized to placebo or to oral doses of two com­pounds:

Nicotinomide is a vitamin B3 amide that is a precursor for nicotinamide adenine dinucleotide (NAD+). NAD+ is a key intracellular molecule involved in mitochondrial production of energy and in redox metabolism. As nicotinamide levels in sera decline with age, the investigators hypothesized that increasing the availabil­ity of nicotinamide (and, as a result, NAD+) might prevent flagging RGCs from progressing further toward apoptosis, Dr. Liebmann said.

Pyruvate is a compound that can overcome ocular deficits in glycolysis. It also acts as an antioxidant in the retina and aids oxidation and adenosine triphosphate production in RGCs and other cells. Animal studies have shown that levels of retinal pyruvate fall in re­sponse to high IOP and that this decrease occurs before detectable optic nerve degeneration.

Results. The participants were followed for a median of 2.2 months. Visual field tests performed during this time showed that the number of improving test locations was higher in the treatment group than in those who received placebo (p = .005).

Looking ahead. Buoyed by the early hints of efficacy, the investigators are planning to follow up with a larger, longer-term clinical trial to gauge the effectiveness of this strategy.

Dr. Liebmann noted that his pa­tients, who often follow the glaucoma literature, have begun asking him about taking nicotinomide and pyruvate. “They want to know how much to take. But I try not to encourage too many people to use it, as our data are very limited. We will know much more in the next two years.” If pressed, Dr. Liebmann recommends nicotinamide 1,000 mg daily, divided into two equal doses. Although participants in the dos­ing trial received up to 3,000 mg daily with no serious adverse events, longer studies are needed to rule out down­stream adverse effects with larger doses, he said.

—Linda Roach

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1 De Moraes CG et al. JAMA Ophthalmol. Pub­lished online Nov 18, 2021.

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Relevant financial disclosures: Dr. Liebmann—Allergan: C; Diopsys: O; Galimedix Therapeutics: C,O; Thea Pharmaceuticals: C.

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