Very weak evidence from clinical trials indicates that LOLA treatment may benefit people with hepatic encephalopathy. LOLA lowers ammonia levels by increasing the generation of urea through the urea cycle, a metabolic pathway that removes ammonia by turning it into the neutral substance urea. LOLA may be combined with lactulose and/or rifaximin if these alone are ineffective at controlling symptoms. Epidemiology and prognosis
In those with cirrhosis, the risk of developing hepatic encephalopathy is 20% per year, and at any time about 30–45% of people with cirrhosis exhibit evidence of overt encephalopathy. The prevalence of minimal hepatic encephalopathy detectable on formal neuropsychological testing is 60–80%; this increases the likelihood of developing overt encephalopathy in the future. Once hepatic encephalopathy has developed, the prognosis is determined largely by other markers of liver failure, such as the levels of albumin (a protein produced by the liver), the prothrombin time (a test of coagulation, which relies on proteins produced in the liver), the presence of ascites and the level of bilirubin (a breakdown product of hemoglobin which is conjugated and excreted by the liver). Together with the severity of encephalopathy, these markers have been incorporated into the Child–Pugh score; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation.In acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis.
Although renal toxicity was not observed in the clinical studies with golodirsen, potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Renal function should be monitored in those taking golodirsen. Pharmacology
Pharmacokinetics
Following single or multiple intravenous infusions, the majority of drug elimination occurs within 24 hours of intravenous administration. The elimination half-life of golodirsen, in parity with eteplirsen was 3 to 6 hours. Clinical benefits
As a first-generation drug, golodirsen is far away from being curative; clinical trial outcomes have demonstrated the drug to have a marginal effect on ameliorating DMD pathology. As of December 2019, golodirsen is approved for therapeutic use in the United States, as well as in the countries that automatically recognize the decisions of the US Food and Drug Administration, under the condition that its benefit will be demonstrated in a confirmatory clinical trial. Society and culture
Golodirsen is one of the very few FDA-approved exon-skipping therapy for Duchenne muscular dystrophy (DMD), although the clinical benefits of the drug are yet to established. While the development of golodirsen needed huge financing, it is only applicable to a small subset of DMD patients. Sarepta Therapeutics has announced that golodirsen will cost in parity with eteplirsen, another drug of a similar kind, which may be as high as US$300,000 a year. Whether the patients should spend so much on a drug with questioned efficacy raises concerns.