Methods of modulation of branched chain acids and uses thereof
View Patent ↗A method of modulating plasma levels of branched chain amino acids and branched chain alpha-keto acids is disclosed, wherein an ammonia scavenger compound or a salt thereof, for example phenylbutyrate or an even numbered congener thereof or a salt thereof, is administered to an individual in need thereof. In various methods, a decrease in plasma levels of branched chain amino acids and branched chain alpha-keto acids is effected to treat individuals suffering from an inborn error in metabolism of amino acids, such as Maple Syrup Urine Disease, for example.
1. A method of treating an individual for maple syrup urine disease (MSUD), comprising the step of administering a therapeutically effective amount of sodium phenylbutyrate to the individual.
2. The method of claim 1 , wherein said MSUD is selected from the group consisting of the classical form, the intermediate form, the intermittent form and the thiamine-responsive form of the disease.
3. The method of claim 1 , wherein said compound is administered orally, intra-peritoneally or intravenously.
4. The method of claim 1 , further comprising restricting the dietary branched chain amino acid intake in said individual.
5. The method of claim 1 , wherein said phenylbutyrate causes decreased phosphorylation of the S293 and S303 residues of the E1α subunit of the branched chain dehydrogenase enzyme complex protein.
6. A method of reducing high plasma levels of branched chain amino acids in an individual, comprising the step of administering a therapeutically effective amount of sodium phenylbutyrate to the individual, wherein the high plasma levels of branched chain amino acids is compared to levels of branched chain amino acids in a healthy individual.
7. The method of claim 6 , wherein said branched chain amino acids are at least one of leucine, isoleucine and valine.
8. The method of claim 6 , wherein said high plasma levels of branched chain amino acids are due to an inborn error of metabolism.
9. The method of claim 6 , wherein said compound is administered orally, intra-peritoneally or intravenously.
10. The method of claim 6 , further comprising restricting the dietary branched chain amino acid intake in said individual.
11. The method of claim 6 , wherein said phenylbutyrate causes decreased phosphorylation of the S293 and S303 residues of the E1α subunit of the branched chain dehydrogenase enzyme complex protein.