Treatment of Cardiac Disorder with Nicotinamide Riboside

Technology Overview

Mitochondria supply energy for cells, including the energy needed by cardiomyocytes for repeated heart muscle contraction. Mitochondria also synthesize crucial iron co-factors, such as iron-sulfur clusters and heme that are necessary for proper mitochondrial function. Iron itself, is vital for several processes such as oxygen transport and oxidative phosphorylation. Hence, the biogenesis and maintenance of mitochondria, including the removal of dysfunctional mitochondria through mitophagy and the synthesis of iron co-factors is important for proper cardiomyocyte function.

Improper cardiomyocyte function may lead to heart failure. Mitochondrial dysfunction has been shown to result in a drop in NAD/NADH ratios, which in turn, negatively affects mitochondrial biogenesis and mitophagy. Similarly, up to 50 % of patients with heart failure have iron deficiency, which is associated with poor outcomes despite current therapies.

The inventors have used a mouse model for cardiomyopathy wherein, the mice have moderately iron-deficient hearts, without affecting the rest of the body. They then tested a known compound, NR that has been shown to robustly increase NAD/NADH ratios. They found that untreated mutant mice lived for 10-10.5 days, while those treated with NR survived on average for 11-15 days. This roughly 50 % increase in lifespan serves as a proof of concept for the treatment of cardiopathology with NR.

Potential Applications

Patients with cardiac disorders that have low iron and NAD/NADH levels could be treated with therapeutically effective amounts of NR alone, iron alone, or a combination of NR and iron.

Advantages

NR has already been used in humans with no known toxicities.