One Year Experience of Pheburane (R) (Sodium Phenylbutyrate) Treatment in a Patient with Argininosuccinate Lyase Deficiency

WOS: 000376982900005PubMed ID: 25665834Argininosuccinate lyase deficiency (ASLD) is a urea cycle disorder (UCD) treated with dietary adjustment and nitrogen scavenging agents. "Pheburane (R)" is a new tasteless and odour-free formulation of sodium phenylbutyrate, indicated in the treatment of UCD. A male patient diagnosed with ASLD was put on treatment with the new formulation of sodium phenylbutyrate (granules) for a period of one year, at 500 mg/kg orally in 3 intakes/day. Plasma glutamine, arginine, citrulline, argininosuccinate, serum sodium, potassium, liver function tests and urine orotate all remained unchanged over this period. There was no difference in mean ammonia levels before and after treatment, and no hyperammonemia episode occurred during treatment with Pheburane (R). An improvement in a measurement of quality of life (QOL) was noted after treatment with Pheburane (R) r. Conclusion: Good metabolic control and improved QOL were achieved throughout the treatment period

Proteostasis in cardiac health and disease

The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting