Nicotinamide Riboside for the Prevention and Treatment of Hearing Loss

Background & Unmet Need

• Noise exposure is a major cause of hearing loss, which lacks effective treatment or prophylaxis
• Following noise exposure, hair cells release neurotransmitters that lead to excitotoxic damage to the neurites, resulting in synaptic disruption and neurite retraction
• Nicotinamide adenine dinucleotide (NAD+) exhibits axon-protective effects in cultured neurons, but its ability to block degeneration in vivo is confounded by poor cell permeability and serum instability
• Unmet Need: Novel neuroprotective therapeutics that prevent against hearing loss after noise exposure

Technology Overview

• The Technology: Method of preventing and treating hearing loss by administering agents that increase intracellular NAD+ levels
• Discovery: Augmentation of intracochlear NAD+ levels protects mice from noise-induced hearing loss (NIHL)
• Administration of nicotinamide riboside (NR) provides an efficient route to increase NAD+ levels in the cochlea in mice and protects from NIHL
• NR also prevented retraction of spiral ganglia neurites from the inner hair cells, demonstrated that NR activates a NAD+-SIRT3 pathway that reduces neurite degeneration caused by noise exposure

Technology Applications

• Therapeutic agents for preventing and treating hearing loss
• Method to determine if a compound acts as a hearing protective agent

Technology Advantages

• Nicotinamide riboside, an NAD+ precursor, overcomes the cell permeability and serum instability challenges of directly administering NAD+
• May be given prophylactically to patients at high risk of hearing loss (e.g., musicians, construction workers)