Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) (NMNAT1)

Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is a nuclear enzyme that plays a vital role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for cellular energy metabolism, DNA repair, and cell signaling [UniProt: Q9UKG1]. It specifically catalyzes the conversion of nicotinamide mononucleotide (NMN) and ATP into NAD+ [NCBI Gene: 4820]. Mutations in the NMNAT1 gene are the underlying cause of Leber Congenital Amaurosis type 9 (LCA9), a severe form of early-onset retinal degeneration that leads to profound vision loss due to the death of photoreceptor cells [PubMed: 22842230]. Gene augmentation therapy, such as the investigational candidate OCU410ST, aims to deliver a functional copy of the NMNAT1 gene to the retina using an adeno-associated virus (AAV) vector to restore NAD+ levels and preserve visual function [Ocugen]. Beyond its metabolic function, NMNAT1 is recognized for its significant neuroprotective properties, particularly in preventing axonal degeneration in various neurodegenerative contexts [PubMed: 33105454]. This target is currently a focus of precision medicine efforts to treat inherited blindness by addressing the specific genetic deficit in LCA9 patients [PubMed: 35653474].

Other names

NMN adenylyltransferase 1PNAT1LCA9NaMN adenylyltransferase 1Nicotinamide-nucleotide adenylyltransferase 1

Gene augmentation therapy involving the delivery of a functional NMNAT1 gene via a viral vector to restore enzymatic activity and NAD+ homeostasis.