Dihydronicotinamide Riboside Derivatives for the Treatment of Neurodegeneration and Neuronal Injury

Background & Unmet Need

• Increasing NAD+ production has been shown to provide numerous health benefits in animal models of human disease
• However, directly administering exogenous NAD+ is challenging due to the requirements of high doses and poor cell permeability and serum instability
• Unmet Need: Therapeutic approaches to increase endogenous production of NAD+ with improved pharmacological and pharmacokinetic properties

Technology Overview

• The Technology: Dihydronicotinamide riboside (NRH) derivatives that are robust enhancers of NAD concentration with no apparent toxicity
• The NRH derivatives were synthesized using nicotinamide riboside (NR) and NR esters as starting points, with high yields
• PoC Data: The NRH derivatives were robust enhancers of NAD+ concentration in cultured mammalian cells (200-1000% NAD+ increase over untreated controls)
• No apparent toxicity was observed with the NRH derivatives
• The NRH derivatives enabled cells to resist toxicity caused by hydrogen peroxide and a DNA-damaging agent, demonstrating efficacy in cell protection

Technology Applications

• Reagents for enhancing NAD+ concentrations in biological systems
• Therapeutic agents for treating disease states where increasing NAD+ concentration may be beneficial, such as neuronal injury and neurodegenerative states

Technology Advantages

• The NRH derivatives are strong enhancers for increasing NAD+ concentrations
• No observed toxicity in animal studies
• Enhanced lipophilicity improves drug absorption and penetration of the blood-brain barrier