The KomIT platform at the German Diabetes Center (Leibniz Institute) has conducted extensive research on the hepato-protective function of positive allosteric modulators (PAMs) of the GABA-A receptor that exhibit low BBB penetration.
Using a model of lipotoxic injury it was shown that certain PAMs i) block apoptosis of hepatocytes, ii) reduce ER stress, and iii) inhibit inflammation. A 90 days Tox study showed no adverse events at low and medium dose. An application patent for treating NAFLD/NASH with GABA-A receptor PAMs has been filed.
Work on the molecular targets and the anti-fibrotic activity of these compounds is ongoing including differentiation from GLP-1 receptor analogues (e.g. semaglutide).
The key goal of CureDiab is the development of novel GABA-A receptor PAMs as a first-in-class therapy of NAFLD/NASH.