12 Aug Niagen Bioscience SVP Explains: From NR to NB4168: How Nicotinamide Riboside Research Led to a Pharmaceutical Candidate for Ataxia-Telangiectasia
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MedicalResearch.com Interview with:
Andrew Shao, PhD
Senior Vice President, Niagen Bioscience
Dr. Andrew Shao, PhD
MedicalResearch.com: What is NR and how does it differ from NAD+?
Dr. Shao: NAD (nicotinamide adenine dinucleotide) is a vital coenzyme found in every cell, essential for energy production and DNA repair. While levels decline with age, direct NAD+ supplementation is ineffective because the molecule is poorly absorbed and utilized when taken orally. NR (nicotinamide riboside) is a vitamin B3 derivative and an efficient NAD+ precursor — a “building block” of NAD+. Unlike direct NAD+, NR is readily converted into NAD+ through established metabolic pathways. Pharmacists are ideally positioned to help patients understand that when they seek NAD+ supplements, they actually need an effective precursor like NR.
MedicalResearch.com: Please explain the condition of Ataxia-Telangiectasia. How is it transmitted and what are the clinical manifestations?
Dr. Shao: Ataxia-Telangiectasia (A-T), or Louis-Bar syndrome, is a progressive autosomal recessive neurodegenerative disorder caused by mutations in the ATM gene. This gene encodes a kinase critical for DNA repair, genomic stability, and mitochondrial function. As a recessive trait, there is a 25% risk of offspring carrying the mutation if both parents carry the mutation. Clinically, A-T manifests as progressive ataxia (loss of motor coordination), telangiectasias (enlarged blood vessels on the skin and eyes), and immunodeficiency. Early signs include unsteady gait and impaired eye movement. Due to defective DNA repair and mitochondrial dysfunction, patients are highly susceptible to cancers, recurrent respiratory infections, and steady neurological decline.
MedicalResearch.com: How does NB4168 differ from NR and NAD+?
Dr. Shao: To understand the distinction, it is helpful to look at both the biophysical limitations of direct NAD+ and the pharmacokinetics of traditional precursors. First, NAD+ is an intracellular coenzyme, meaning it is produced and exerts its function within cells. Direct, exogenous NAD+ is not bioavailable, as it is a bulky, highly charged molecule that cannot efficiently cross cellular membranes intact. When administered systemically or orally, direct NAD+ must be broken down into smaller nucleosides or building blocks, such as nicotinamide riboside (NR), before entering cells to be converted back into intracellular NAD+. Standard NR overcomes this barrier by using specialized nucleoside transporters to enter cells directly and fuel NAD+ synthesis. While supplemental NR (such as Niagen) is highly effective for general health and wellness, pharmaceutical applications for severe genetic neurodegenerative conditions may require significantly higher systemic exposure and differentiated kinetics.
NB4168 is our next-generation, proprietary small-molecule pharmaceutical candidate designed specifically to address these elevated therapeutic demands. Protected by composition-of-matter patents, NB4168 is engineered to optimize oral delivery and achieve substantially higher systemic delivery of NR in the bloodstream than conventional NR formulations. The intent is to facilitate greater availability of the active drug moiety in A-T patients and augment depleted NAD+ levels. Ultimately, it gives us a targeted, small molecule candidate that’s ready for the FDA’s regulatory process.
MedicalResearch.com: What might be the role of NB4168 in the treatment of Ataxia-Telangiectasia?
Dr. Shao: NB4168 is designed to directly target the underlying metabolic collapse driven by ATM gene deficiency. In A-T, persistent unrepaired DNA damage triggers continuous overactivation of poly (ADP-ribose) polymerases (PARPs) — a group of NAD+-consuming enzymes — a process that consumes and depletes intracellular NAD+ stores. This metabolic depletion triggers a cascade of mitochondrial failure, impaired mitophagy, elevated oxidative stress, and neuroinflammation, ultimately driving premature cell death in cerebellar neurons. By safely delivering significantly higher systemic exposure of NR to the bloodstream, NB4168 efficiently replenishes intracellular NAD+. Restoring this vital coenzyme helps break the pathological cycle by re-energizing cellular bioenergetics, promoting mitochondrial quality control, and mitigating neuroinflammatory signaling.
From a clinical standpoint, NB4168 aims to translate the promising proof of concept observed with NR in early human studies into a standardized, small molecule pharmaceutical therapy. Independent clinical trials evaluating NR supplementation in A-T cohorts have already demonstrated meaningful improvements in motor coordination, as assessed by validated clinical endpoints such as the RmICARS scale, along with stabilization of ocular movements and immune markers. Supported by its FDA Rare Pediatric Disease and EMA Orphan Medicinal Product designations, NB4168 is designed to optimize these therapeutic benefits by enhancing pharmacokinetics. Our ultimate objective is to offer a disease-modifying treatment that preserves neurological function, slows disease progression, and fills a critical unmet need for A-T patients and their families.
MedicalResearch.com: What are the risks associated with NR/NAD+ treatment? Are there contraindications to their use or potential drug interactions?
Dr. Shao: Decades of preclinical research and dozens of human clinical trials have established that Nicotinamide Riboside (NR, as Niagen) possesses a remarkably wide margin of safety. Unlike classical forms of vitamin B3, such as niacin, which frequently causes uncomfortable cutaneous flushing, dizziness, and, at high doses, hepatic stress or elevated uric acid, NR elevates intracellular NAD+ without triggering vasodilatory side effects or liver toxicity. In randomized, double-blind, placebo-controlled trials across diverse age groups, NR was exceptionally well tolerated. Reported adverse events are generally mild, infrequent, and non-distinguishable from placebo, typically consisting of transient, mild gastrointestinal discomfort or low-grade headache at elevated doses. Extensive toxicology studies and regulatory evaluations have earned NR FDA Generally Recognized As Safe (GRAS) status and multiple New Dietary Ingredient (NDI) notifications.
Regarding contraindications and drug interactions, standard dietary NR shows no known inhibition of major cytochrome P450 enzymes or adverse pharmacodynamic cross-reactivity. However, as a matter of clinical prudence, certain patient populations require specialized medical oversight. For instance, those diagnosed with cancer should check with their physician prior to using NAD+ supplements. For pharmaceutical candidates like NB4168 destined for orphan pediatric indications, formal drug-interaction and safety profiling are being assessed in our IND-enabling preclinical protocols to ensure patient safety.
Disclosures: Dr. Shao is Senior Vice President of Niagen Bioscience.
For a broader overview of how NR, NMN, and other NAD+ precursors compare for healthy aging and longevity research, see this MedicalResearch.com overview of NAD+ vs NMN vs resveratrol supplements for healthy aging.
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Last Updated on August 12, 2026 by Marie Benz MD FAAD