Threonate compounds and methods of use thereof

Abstract

Provided herein is a method of using threonate to alter cellular physiology, such as neuronal physiology. A method of the present disclosure may include providing to a medium comprising a cell, a threonate-containing compound, or a precursor thereof, to increase the concentration of threonate in the medium, where the increased concentration of threonate is sufficient to increase the concentration of magnesium in the cell. Also provided is a method that includes administering a threonate-containing compound, or a precursor thereof, to an individual, to increase synaptic density in the brain and/or to treat a neurological disorder, e.g., cognitive impairment. The threonate-containing compound of the present disclosure does not include magnesium threonate.

1 . A method of increasing brain synaptic density of an individual, comprising:
 administering to an individual a first dosage form comprising an effective amount of a threonate-containing compound, or a precursor thereof, to increase synaptic density in one or more regions of the brain of the individual,   wherein the threonate-containing compound, or precursor thereof, is not a magnesium salt.   
     
     
         2 . The method of  claim 1 , wherein the threonate-containing compound, or precursor thereof, is a monovalent, divalent or trivalent cation salt, or precursor thereof, of threonate. 
     
     
         3 . The method of  claim 2 , wherein the monovalent, divalent or trivalent cation is selected from the group consisting of: H + , Li + , Na + , K + , Ca 2+ , NH 4   + , C 1 -C 8  monoalkylammonium, C 2 -C 8  dialkylammonium, C 3 -C 8  trialkylammonium, and Fe 3+/2+ . 
     
     
         4 . The method of  claim 1 , wherein the administering comprises administering the first dosage form orally, intravenously, or transcutaneously. 
     
     
         5 . The method of  claim 1 , wherein the method further comprises co-administering a second dosage form comprising magnesium with the first dosage form. 
     
     
         6 . The method of  claim 1 , wherein the one or more regions of the brain comprise the hippocampus, cortex, amygdala, and/or the basal ganglion. 
     
     
         7 . The method of  claim 1 , wherein the first dosage form comprises one or more additional agents selected from the group consisting of a pharmacological agent, a flavoring agent, a coloring agent, a sweetening agent, a filling agent, a binding agent, a lubricating agent, an excipient, and a preservative. 
     
     
         8 . A method of increasing intracellular magnesium concentration, comprising:
 providing to a medium comprising a cell, a threonate-containing compound, or a precursor thereof, to increase the concentration of threonate in the medium, wherein the increased concentration of threonate is sufficient to increase the concentration of magnesium in the cell compared to the concentration of magnesium in the cell before the providing,   wherein the threonate-containing compound, or precursor thereof, is not a magnesium salt.   
     
     
         9 . The method of  claim 8 , wherein the cell is in vitro, and wherein the providing comprises contacting the cell with a composition comprising the threonate-containing compound, or a precursor thereof. 
     
     
         10 . The method of  claim 8 , wherein the cell is in vivo, and wherein the providing comprises administering to an individual, a composition comprising the threonate-containing compound, or a precursor thereof, in an amount sufficient to increase the concentration of threonate in an extracellular medium of a cell in the individual. 
     
     
         11 . The method of  claim 8 , wherein the concentration of extracellular magnesium in the medium is in the range of 0.3 mM to 2.0 mM. 
     
     
         12 . The method of  claim 8 , wherein the concentration of magnesium in the cell is increased by 5% or more. 
     
     
         13 . The method of  claim 8 , wherein the concentration of threonate in the medium is 75 μM or more. 
     
     
         14 . The method of  claim 8 , wherein the threonate-containing compound, or precursor thereof, is a monovalent, divalent or trivalent cation salt, or precursor thereof, of threonate. 
     
     
         15 . The method of  claim 14 , wherein the monovalent, divalent or trivalent cation is selected from the group consisting of: H + , Li + , Na + , K + , Ca 2+ , NH 4   + , C 1 -C 8  monoalkylammonium, C 2 -C 8  dialkylammonium, C 3 -C 8  trialkylammonium, and Fe 3+/2+ . 
     
     
         16 . The method of  claim 8 , wherein the cell is a cell that expresses a glucose transporter. 
     
     
         17 . The method of  claim 8 , wherein the cell is a neuronal cell. 
     
     
         18 . The method of  claim 17 , wherein the neuronal cell is a central nervous system neuron. 
     
     
         19 . The method of  claim 18 , wherein the neuron is a hippocampal or cortical neuron. 
     
     
         20 . A method of treating a neurological disorder in an individual, comprising:
 administering to an individual in need of treatment for a neurological disorder, a first dosage form comprising a therapeutically effective amount of a threonate-containing compound, or a precursor thereof, to ameliorate the neurological disorder,   wherein the threonate-containing compound, or precursor thereof, is not a magnesium salt.   
     
     
         21 .- 40 . (canceled)