Nicotinamide Riboside for Treatment of Iron-deficient Heart Failure

Background & Unmet Need

• Nearly 6.7 million Americans above the age of 20 have heart failure, a serious clinical disorder with high mortality rates despite current treatments
• Mitochondria are essential for heart function, and are are abundant in cardiomyocytes to supply energy for repeated muscle contraction
• Mitochondria synthesize certain iron co-factors, iron-sulfur (Fe-S) clusters and heme, which are necessary for mitochondrial function
• Proper maintenance of mitochondria and iron homeostasis is crucial for cardiac cell function, including energy production and oxygen transport
• Up to 50% of heart failure patients are iron deficient, which correlates with poor outcomes
• Unmet Need: New therapeutic approaches for heart failure that address iron deficiency and mitochondrial dysfunction to improve patient outcomes

Technology Overview

• The Technology: Administration of nicotinamide riboside (NR) for treatment of heart failure, especially iron-deficient heart failure
• NR may be delivered alone or in combination with iron therapy
• PoC Data: A mouse model with cardiac-specific iron deficiency demonstrated significantly extended lifespan with NR treatment
• Untreated mice survived 10-10.5 days while NR-treated mice lived 11-15 days (approximately 50% increase in lifespan)
• NR treatment decreased expression of mitochondrial unfolded protein response genes and accumulation of p62, which is associated with mitophagy
• This indicates that NR may improve overall mitochondrial quality or enhance mitophagy, which is important for cardiomyocyte maintenance and function

Technology Applications

• Treatment of heart failure patients, particularly in those with iron deficiency
• Potential combination therapy with iron supplementation for enhanced benefits

Technology Advantages

• NR has established safety profile with no known toxicities in humans
• NR can be administered chronically via simple oral administration

Figure: NR treatment of mice with cardiac-specific iron deficiency increased the lifespan of mice by ~50%.