Variants in a newly discovered microprotein affected the risk of Alzheimer’s disease more than any other known risk variant besides ApoE. The protein, dubbed SHMOOSE by its discoverers, was identified in a mitochondrial-wide association study (miWAS). The researchers reported their findings in the Sept. 21, 2022, issue of Molecular Psychiatry. The newly identified variant is not rare – it occurs in about a quarter of the Caucasian population, slightly more than the ApoE4 allele. Its effects are also not subtle – in their paper, the team estimated that those with the high-risk variant SHMOOSED47N were roughly 30% more likely to develop AD than those without.
Investigators at Washington State University (WSU) have identified a set of eight proteins that were expressed in the serum of Ursus arctos horribilis, better known as the grizzly bear, specifically during their hibernation period. In addition to reporting new basic insights into hibernation, the study, which was published in the Sept. 21, 2022, issue of iScience, could also give clues to insulin resistance and its relationship to body fat.
Pancreatic β cells are the only cells in the body that produce insulin, and are the cells whose malfunctioning is the proximate cause of diabetes. Consequently, repairing or replacing β cells is one of the major goals of diabetes research. In type I diabetes, where the immune system destroys β cells, need to be replaced outright. In type II diabetes, β cells “disappear” in another way. There is ample evidence that under conditions of chronic high blood sugar, such cells dedifferentiate, becoming less β cell-like over time.
As therapeutics development in Alzheimer’s disease (AD) is broadening its search for therapeutic targets, one of the alternatives to amyloid-β, or at least to its direct targeting by monoclonal antibodies, that is coming into focus is triggering receptor expressed on myeloid cells 2 (TREM2). From a drug development standpoint, amyloid-β remains a mystery. Scientific evidence clearly suggests that amyloid misprocessing is an underlying factor in the development of AD, and it is certainly a reasonable hypothesis that reducing amyloid plaque should fight the disease.
Pathogen-associated molecular patterns (PAMPs) are by themselves not enough to set off a full innate immune response to viral infection. Instead, structural changes to the actin cytoskeleton primed the activation of RIG-I-like receptors (RLRs), a family of intracellular RNA sensors that detect many types of viral RNA. When primed RLRs then encountered viral RNA, they set off an innate immune response that led to the production of interferons.
Using a two-drug combination, researchers at the University of California at San Francisco (UCSF) have been able to achieve brain-specific inhibition of several kinases.
The gamma secretase inhibitor nirogacestat (Springworks Therapeutics Inc.) reduced the risk of disease progression by roughly 70% in a randomized placebo-controlled phase III trial in patients with desmoid tumors.
Data presented Sept. 9 at the European Society of Medical Oncology 2022 Congress showed impressive effects for KRAS inhibitors. But they also illustrated their limitations. Earlier-stage trials and researcher presentations, meanwhile, suggested ways those limitations might be addressed. Results from the Codebreak 200 study, presented in the day’s Presidential Symposium, were typical of the best that targeted therapies have to offer: large effects for brief time periods.
Scientifically at least, the biggest story coming out of the European Society for Medical Oncology (ESMO) 2022 Congress is the success of cell therapy in solid tumors. “During this ESMO, there is a lot of novelty coming from T-cell therapies,” John Haanen told the audience at his joint keynote speech with Ton Schumacher – so much so that Haanen and Schumacher, both group leaders at the Netherlands Cancer Institute, left antibodies out of their keynote session in order to do justice to the advances in cell therapies.
“The association between air pollution and lung cancer is not new,” Charles Swanton told the audience at the European Society of Medical Oncology (ESMO) 2022 Congress. But as with so many associations, causation has been hard to establish, partly due to the puzzling absence of mutations.
