D-Amino Acids for NAFLD Drug

~Oral D-Cysteine shows inhibitory effects on hepatic disorders~


  • Solutions to areas of global prevalence of 25% with no specific treatment
  • Approach with amino acid which has established mass production and high solubility
  • Confirmed that the concentration of 500 mg/kg shows an inhibitory effect

Current Stage & Goals

Non-alcoholic fatty liver disease (NAFLD) is a liver disease in which lipids accumulate in the liver regardless of alcohol consumption, with an estimated high incidence of about 25% in adults. 10-20% of patients with NAFLD require treatment because they develop nonalcoholic hepatitis, which carries a high risk of cirrhosis and liver cancer, but no curative treatment is currently established.
Recently, hydrogen sulfide, which is produced in trace amounts in the body, has been reported to have protective effects against NAFLD. Hydrogen sulfide is produced in vivo when D-cysteine, one of D-form amino acids, is metabolized by the enzyme D-amino acid oxidase (DAO).
The inventors hypothesized that D-cysteine exerts its therapeutic or preventive effects against NAFLD by producing hydrogen sulfide in the liver through DAO metabolism. They demonstrated that D-cysteine suppresses adipose-derived reactive oxygen species by the biosynthesis of hydrogen sulfide through DAO metabolism in vitro and inhibits liver injury in vivo.


Effects of D-Cysteine in a mouse model of NAFLD expressing hepatic DAO

Since DAO is expressed in the liver in humans but not in mice (except in the kidney and cerebellum), an adeno-associated viral (AAV) vector that selectively expresses DAO in the liver was injected into the target mice via the tail vein to create the same conditions as in humans. After 4 weeks, we confirmed that DAO was expressed in the livers of mice injected with DAO-expressing AAV vectors but was not expressed in the livers of control mice. Thereafter, these mice were fed a normal or high-fat diet, while D-Cysteine or saline was orally administered every day for 4 weeks. During this period, blood samples were drawn weekly to measure AST and ALT levels.


Chronic administration of D-Cysteine suppressed the elevation of AST and ALT in the high-fat low-methionine choline diet (HFLMCD) group.

D-Cysteine significantly suppressed AST from the second week onward and ALT from the third week onward.


Pending (unpublished)


National University Kumamoto University


Himeji Dokkyo University  Department of Pharmacology, Faculty of Pharmaceutical Sciences
Professor Takahiro Seki

Development Phase

This stage  : Proof of concept for NAFLD suppression effect by D-Cysteine is completed
Next stage :
1) Mechanism research, Development drug optimization
2) Clinical development

We are looking for partner companies interested in commercialization or in collaborations about this NAFLD drug. We would be happy to start with a detailed explanation and discussion of the technology.


Project No.ON-04751



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