INDY inhibition attenuates diet-induced NASH

Eternygen presents data positioning mINDY inhibitors as novel therapeutic option in NASH

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BERLIN—Eternygen GmbH, a privately owned metabolic diseases company, announced in February the presentation of data at the Third Global NASH Congress held in London that month. The presentation provided data from a preclinical study which demonstrates that inhibiting the plasma-membrane tricarboxylate transporter INDY (I’m Not Dead Yet/NaCT), encoded by the longevity gene mIndy/SLC13A5 and using a small molecule, is able to reverse nonalcoholic steatohepatitis (NASH) in a diet-induced NASH mouse model.
INDY inhibition (INDYi) significantly reduced transaminase levels ALAT by 59 percent and ASAT by 39 percent, indicating reduced liver injury. Hepatic triglyceride accumulation was decreased by 31 percent. Moreover, fluorescence-activated cell sorting (FACS) analysis for intrahepatic immune cells showed marked reduction in total number of both lymphoid and myeloid cells—for example, monocyte-derived macrophages, Kupffer cells and monocytes were reduced by 73 percent, 66 percent and 58 percent, respectively.
“For the first time, these studies have validated the therapeutic potential of our target protein INDY in NASH. The data provide proof of concept that regulating intracellular metabolic processes through inhibition of INDY is a feasible approach to treat NASH,” said Dr. Andreas Birkenfeld, one of Eternygen’s scientific founders and a recognized opinion leader in INDY research. “The current understanding of the pathophysiology fits nicely with this mode of action. Based on the new experiments and earlier data in INDY knockout mice, we see a unique profile with beneficial effects on early-stage NASH, as well as on later-stage inflammation and fibrosis, as well as cardiovascular risk factors. These are encouraging results and provide new promise for patients and caregivers.”
Added Marco Janezic, CEO of Eternygen: “These data confirm the unique pleiotropic mechanisms of INDY inhibition in addressing metabolic dysregulation as the root cause of NASH and subsequent complications (including inflammation and fibrosis) as well as validating its role in restoring liver function. We are now evaluating the next development steps necessary to bring this drug candidate into the clinic.”

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