The objective of this proposal is to commercialize treatment for three rare inborn errors of urea synthesis; deficiencies of carbamyl phosphate synthetase, ornithine transcarbamylase and argininosuccinic acid synthetase. These diseases in the their most severe form are fatal in the first months of life an cause mental retardation in the milder cases, all of which are a consequence of a failure to synthesize urea nitrogen and the resulting accumulation of ammonia. The treatment consists of an oral dosage form of sodium phenylbutyrate (IND # 17123) a pro-drug which is beta oxidized to phenylacetate which in turn conjugates with glutamine to yield phenylacetylglutamine which serves a substitute for urea nitrogen as a vehicle for waste nitrogen excretion. An intravenous dosage form is also available using a combination of sodium benzoate and sodium phenylacetate. These drugs have proven to prolong survival in the most serious form of these diseases and prevent deterioration of intelligence in the milder forms of the disease. This proposal is designed to collate and interpret data collected during a FDA phase 3 Investigational New Drug study to assemble and submit New Drug Application will enable the products to be manufactured, marketed and distributed in accordance with Food and Drug Statutes. As a result, patients will have guaranteed and uninterrupted access to an approved drug.
