Researchers from E-Therapeutics plc presented preclinical data for ETX-312, a GalNAc-conjugated short interfering RNA (siRNA), produced using the Galomic platform and being developed for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).
A ketone body, a molecule derived from the metabolism of acids to obtain energy when glucose is not available, could become an effective ally in treating Alzheimer’s or preventing the effects of aging on the brain. A group of scientists at the Buck Institute for Research on Aging have studied the role of β-hydroxybutyrate (βHB) as a signaling metabolite of misfolded proteins by interacting with them and altering their solubility, a mechanism that allows their elimination, as observed in preclinical models.
A U.K. study has uncovered distinctive genetic drivers of type 2 diabetes in South Asians that lead to faster development of complications, the need for earlier insulin replacement therapy and a weaker response to some widely prescribed drugs. That points to the need to refine care pathways. But in addition, the research provides a potent illustration of how the under-representation in genomics databases of people who are not of white European origin can skew results and be a source of discrimination.
Recently presented preclinical data show that EA Pharma Co. Ltd.'s EA-3571 is a highly potent dual inhibitor of enteropeptidase and trypsin with luminal action, resulting in potential anti-insulin resistance and fat-burning properties.
Potent siRNAs against B4GALT1 were designed in silico and screened in vitro (Huh7 cells, primary mouse, human hepatocytes) as well as in vivo (C57BL/6 mice) for the selection of a lead Galomic siRNA.
Researchers at the University of Copenhagen have identified a signaling pathway that simultaneously increased energy expenditure and decreased food intake. In both human and primate studies, agonists of the tachykinin NK2 receptor (NK2R) led to both decreased food intake and increased energy expenditure. And in behavioral tests, they were not aversive, suggesting they do not cause the nausea that is a major side effect of GLP-1 agonists.
Urocortin-2 (UCN2) is a selective corticotropin-releasing factor CRF2 receptor (CRFR2) agonist, which has been previously shown to reduce fat mass while promoting muscle hypertrophy. Hanmi Pharmaceutical Co. Ltd. presented the discovery and preclinical characterization of a novel CRFR2-selective UCN2 analogue, HM-17321, being developed for the treatment of obesity.
Startup company Pep2tango Therapeutics Inc., unveiled with backing by Versant Ventures, is advancing unimolecular multireceptor peptide agonists that target GLP-1, GIP, amylin and calcitonin receptors.
Fat cells from patients who had lost weight after bariatric surgery, as well as from animals who had gained and then lost weight, were transcriptionally distinct from cells that had not experienced such weight changes at the organism level. In the animal studies, those transcriptional changes were due to epigenetic changes. The findings, which were published online in Nature on Nov. 18, 2024, are a possible molecular-level explanation for the short-term nature of most weight loss.
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