Author:
Stan Tiberiu Loredan,Vijver Davy v.d.,Verhaart Ingrid E.C.,Aartsma-Rus Annemieke
Abstract
AbstractBACKGROUNDVitamin B3 analogue nicotinamide riboside (NR) has been suggested to have beneficial effects on muscle pathology in a mouse model for Duchenne muscular dystrophy (DMD). In muscle dystrophy, NR is thought to act acts by increasing levels of NAD+, to improve mitochondrial functioning and reduce muscle pathology.OBJECTIVEWe here aimed to validate the effects of NR to improve muscle quality after eight weeks of treatment in two different mouse models for DMD: the commonly used mdx mouse on a C57BL/10 background (BL10mdx) and the more severely affectedmdxmouse on a DBA/2J background (D2-mdx).METHODSTo study in more detail whether NR treatment had an impact on muscle pathology, we assessed the expression levels of several markers for DMD pathology (fibrosis, regeneration and inflammation) in diaphragm.RESULTSOur data showed a trend for increase in NAD+-levels in blood; only in the D2-mdxNR-treated mice the NAD+-levels were slightly increased. These markers were elevated inmdxmodels compared to controls, but not affected by the NR treatment. Histological analysis of muscle tissues indicated a mild treatment effect in D2-mdxmice.CONCLUSIONSBased on our results, testing NR treatment in clinical trials in DMD patients is not warranted.
Publisher
Cold Spring Harbor Laboratory