GW and Tel Aviv University researchers developed a small peptide, ND-13, for treatment of chronic kidney disease (CKD). The only current treatment of CKD and end-stage renal disease is renal replacement therapy via dialysis or kidney transplantation. There remains a need to provide alternative therapies for treating kidney disorders. ND-13 contains 7 amino acids to help with cell penetration, plus 13 amino acids from the chaperone protein DJ-1. DJ-1 is expressed in kidney among other tissues and is involved in regulating cell growth and anti-oxidant defense. DJ-1 silencing leads to hypertension and DJ-1 overexpression protects against renal cell damage.
An inflammatory/oxidative environment in a kidney leads to a vicious cycle, which may produce fibrosis and induce renal damage and kidney dysfunction. DJ-1 and ND-13 prevents the ubiquitination of Nrf2 and amplifies its response. Nrf2 may attenuate the oxidative stress and inflammation, leading to a reduced cytokine expression and preventing inflammation, resulting in protection of the renal function. In mouse models, ND-13 protects against renal injury, inflammation and fibrosis. Activation of Nrf2 through this pathway is dependent on oxidation, so may avoid side effects contributed to chronic activation of Nrf2. The researchers continue to validate the treatment in further mouse models.
In addition to the patent below, GW is leading licensing for renal treatment of the issued composition of matter patent for ND-13 itself, US 8,212,001.
Figure. ND-13 protects mice from kidney fibrosis in the event of kidney injury (UUO). * p<0.05 vs. sham † p<0.05 vs. UUO + vehicle
De Miguel C, et al. Int J Mol Sci. 2020 (PMID: 32987947)