Effects of Nicotinamide Riboside on Spinal and Bulbar Muscular Atrophy (SBMA): Preclinical Findings

Synopsis

Previous studies have shown that in spinal and bulbar muscular atrophy (SBMA), a mutant protein called polyQ-expanded AR becomes improperly acetylated, and activating SIRT1, an NAD-dependent enzyme, can protect cells. Based on this, researchers tested whether boosting NAD+ with nicotinamide riboside (NR) could help SBMA mice after symptoms appeared. While NR slightly increased NAD+ in the spinal cord, it did not improve NAD+ or energy levels in muscle or slow disease progression. Further analysis revealed that key energy pathways in muscle, including the NAD+ salvage pathway, were disrupted, partly due to lower levels of Nmrk2, an enzyme needed to use NR. These results suggest that NAD+ is severely reduced in SBMA muscle and that NR treatment alone cannot overcome this deficit because the machinery to use it is impaired.

Journal

JCI Insight