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In some embodiments, the invention encompasses contacting one or more NNMT inhibitors (such as a cation of Formula I or IA, or otherwise disclosed herein) is contacted with a cell expressing NNMT concurrently with one or more chemical entities (e.g., nicotinamide riboside, nicotinamide mononucleotide) that modulate intracellular NAD+ levels to provide muscular therapy

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In further embodiments, the tonicity agents are present in an amount as to provide a final osmolality of an otic formulation or composition of about 100 mOsm/kg to about 500 mOsm/kg, from about 200 mOsm/kg to about 400 mOsm/kg, from about 250 mOsm/kg to about 350 mOsm/kg or from about 280 mOsm/kg to about 320 mOsm/kg