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Targeting NAD+ Synthesis via inhibition of ACMSD to prevent NAFLD and AKI

Nov 28, 2018

Publishing in Nature, scientists lead Johan Auwerx at EPFL (Lausanne) and Roberto Pellicciari at TES Pharma have found a new way of increasing nicotinamide adenine dinucleotide (NAD+) in the kidney and liver. Low levels of NAD+ are associated with age-related diseases, such as: non-alcoholic fatty liver disease (NAFLD) and acute kidney injury (AKI). By inhibiting the enzyme, α-amino-β- carboxymuconate-ε- semialdehyde decarboxylase (ACMSD) NAD+ levels can be restored via the de novo NAD+ synthesis pathway.

The novel patented inhibitors of ACMSD developed by TES Pharma, in collaboration with Prof. Auwerx at the École Polytechnique Fédérale de Lausanne (EPFL) and Prof. Raffaelli at the Università Politecnica delle Marche (UNIVPM) were previously reported in the Journal of Medicinal Chemistry, as the first reported druggable ACMSD inhibitors. Our compounds increase NAD+ levels in a tissue-specific manner and provide protection in disease models of both AKI and NAFLD.

“Inhibiting the activity of ACMSD is a highly innovative way to boost NAD+ levels” say researchers Roberto Pellicciari and Johan Auwerx, “we expect to exploit the NAD+ boosting activity of ACMSD inhibitors in the clinic to treat kidney and liver diseases which represent large unmet medical needs and are often linked with abnormal mitochondrial function.”

Our work has been highlighted many scientific news services, including Nature News & Views, Nature Review Nephrology, and Biocentury, and received extensive media coverage, including newspaper as Le Temps, the Daily Mail, and websites as MyScience, Health Canal, Ebiotrade, Science Daily, Bionity, EurekAlert! and for its potential application as an anti-ageing approach.