July 26 preclinical Quick Takes: Ribon's new mechanism for PARP inhibitors, a microbiome-ALS link and more

Ribon co-founder reports new mechanism for PARP inhibitors
An University of Texas Southwestern team led by Ribon Therapeutics Inc. (Lexington, Mass.) co-founder W. Lee Kraus reported that PARP inhibitors block ribosome production, and therefore tumor cell growth, by reducing nucleolar localization of DDX21. In a Molecular Cell paper, the team suggested the pathway explains why PARP inhibitors are effective in some cancers lacking mutations in DNA repair pathways and that DDX21 nucleolar localization could be used as a biomarker of clinical response to PARP inhibitors. Ribon plans to move its PARP inhibitors into the clinic this year (see "Ribon Raises $65 Million Series B to Target monoPARPs").

Linking the gut microbiome with ALS symptoms
DayTwo Ltd. (Tel Aviv, Israel) scientific co-founders Eran Elinav and Eran Segal and colleagues reported in a Nature article that low gut levels of the commensal bacteria Akkermansia muciniphila were associated with ALS severity in mice, and low serum levels of nicotinamide, a metabolite associated with the bacteria, were associated with disease severity in ALS patients. Supplementation with A. muciniphila or nicotinamide improved motor function in the mice, suggesting modulation of the gut microbiome could treat ALS. Elinav is also a co-founder of BiomX Ltd. (Ness Ziona, Israel)...