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Nutritional Genomics Uncovers Vitamin B3 Therapy as Curative for NAXD Disease

GSE304377 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/02/06 Platform GPL34290
Summary
Vitamins are essential metabolites that must be obtained from external sources. All 13 vitamins were identified in the early 1900s, a rich era of biochemistry. More recently, they are consumed indiscriminately. We introduce a new nutritional genomics framework that begins with a treatment and identifies all potential disease candidates. Using a genome-wide CRISPR screen at varying vitamin B3 levels, we nominated dozens of diseases for B3-based therapy. The top candidate was NAXD, a proofreading enzyme involved in correcting an aberrant form of NADH (NADHX). Mutations in NAXD cause severe neurodevelopmental disease, with no proven therapies. We created a new mouse model of disease, observing NADHX accumulation and NAD+ depletion in affected organs, leading to impaired serine biosynthesis. Low B3 diets worsened the disease, while B3 supplementation was curative, extending lifespan by more than 20-fold. This work introduces a new approach to nutritional genomics and precision vitamin therapies.
Published in
Vitamin B2 and B3 nutrigenomics reveals a therapy for NAXD disease
Garg A, Blume SY, Huynh H et al. · Cell 2026 · PMID 41747729 · doi:10.1016/j.cell.2026.01.022
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Also filed as BioProject PRJNA1301136 and SRA study SRP606322. Searching any of these in the dataset finder brings you back here.

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