DR Cysteamine for Non-alcoholic Steatohepatitis (NASH)

Non-alcoholic Steatohepatitis (NASH) is a progressive liver disease, with a 25% incidence in obese patients. Approximately 2%-5% of the U.S. population is afflicted with this disease, which can cause cirrhosis, liver failure and end-stage liver disease.1

The incidence of NASH is increasing in the U.S. adolescent population.2, 3, 4

Currently there are no treatment options for NASH. The disease is managed with lifestyle changes such as diet, exercise and weight reduction.

Cysteamine is a precursor of the potent liver anti-oxidant glutathione (GSH) and increasing GSH has the potential to reverse NASH-related liver damage. Glutathione itself, unfortunately, does not enter easily into cells, even when given in large amounts. However, glutathione precursors, such as cysteamine, enter into cells and have been shown to be effective in the treatment of certain conditions by preventing significant GSH depletion.2 Raptor is therefore investigating the use of DR Cysteamine for the potential treatment of NASH.

Development Activities for DR Cysteamine for NASH

Raptor’s Phase 2a clinical trial of delayed-release cysteamine bitartrate (a prototype of Raptor’s DR Cysteamine) showed a marked decline in juvenile NASH patients’ ALT levels during the treatment period with 7 of 11 patients achieving a greater than 50% reduction and 6 of 11 reduced to within normal range. AST levels also saw significant improvements with patients averaging 41% reduction by the end of the treatment phase. The reduction in liver enzymes was largely sustained during the 6 month post-treatment monitoring phase. Other important liver function markers showed positive trends. Levels of cytokeratin 18, a potential marker of disease activity in Non-alcoholic Fatty Liver Disease, decreased by an average of 45%. Adiponectin levels increased by an average of 35% during the treatment period. Reduced adiponectin levels are thought to be a marker of the pathogenesis and progression of NASH. Body Mass Index did not change significantly during both the treatment and post-treatment phases. Delayed-release cysteamine bitartrate demonstrated a strong, favorable safety profile, with mean gastrointestinal symptom scores of 1.1 at baseline and 0.7 after 6 months of treatment using a rating system in which the maximum score of 14 indicates most severe gastrointestinal symptoms.

Raptor is preparing for a Phase 2b clinical trial for the potential treatment of NASH.

Learn more about Raptor’s other clinical programs:

References:

  1. National Digestive Diseases Information Clearinghouse. Nonalcoholic Steatohepatitis. Accessed October 14, 2008.
  2. Te Sligte, K., I. Bourass, J.P. Sels, A. Driessen, R.W. Stockbrugger, and G.H. Kock Non-alcoholic steatohepatitis: review of a growing problem. European Journal of Internal Medicine 2004 15:10-21.
  3. Papandreou, D., I. Rousso, and I. Mavromichalis Update on non-alcoholic fatty liver disease in children Clinical Nutrition 2007 26:409-415.
  4. Strauss, R., S.E. Barlow, and W.H. Dietz Prevalence of adnormal serum aminotransferase values in overweight and obese adolescents The Journal of Pediatrics 2000 136:727-733.
  5. Prescott LF, Critchley JA. The treatment of acetaminophen poisoning. Annu Rev Pharmacol Toxicol. 1983;23:87-101.