Transplanted human glial cells could outcompete human glia in a chimeric mouse model of Huntington’s disease, inducing apoptosis. And younger health cells could outcompete older ones. The findings, which appeared online in Nature Biotechnology on July 17, 2023, help pave the way for testing glial cell transplantation as a therapeutic strategy in neurodegenerative disorders.
In brain research, be it basic or clinical, neurons have long hogged the limelight. But at the 2023 European Meeting on Glial Cells in Health and Disease, neurons take a back seat to glia – cell types that have often been described as support cells and treated as an afterthought, but that play critical roles in all aspects of brain function, including information processing.
With the approval of Aduhelm (aducanumab, Eli Lilly & Co.) and Leqembi (lecanemab, Eisai Co. Ltd.), there are finally amyloid-targeting drugs available for Alzheimer’s disease (AD). What’s not available, though, are rose-colored glasses of the prescription strength that would make these approvals look like AD’s happy ending. The biopharma industry is already well aware of the need for broader horizons. Roughly three-quarters of drugs now in clinical development for AD target neither amyloid-β (Aβ) nor tau. Still, the genetic evidence from familial AD strongly implicates Aβ processing in AD’s origins. In his opening plenary talk at the European Academy of Neurology 2023 annual conference, Thomas Südhof suggested new ways to look at the clinical data.
At the 2023 Annual Congress of the European Academy of Neurology, Mary Reilly described the relationship between bench and bedside as “a continuous circle of translation,” with each cycle beginning with patients and their needs.
It seems unlikely that American poet and civil rights activist Maya Angelou spent much time thinking about translational research. But two quotes of hers capture the essence of the interplay between bench and bedside: “I did then what I knew how to do. Now that I know better, I do better” and “I’ve learned that I still have a lot to learn.” At the 2023 Annual Congress of the European Academy of Neurology, Mary Reilly described the relationship between bench and bedside as “a continuous circle of translation,” with each cycle beginning with patients and their needs.
Artificial intelligence (AI) continues to entice. On the exhibition floor at the 2023 Congress of the European Academy of Neurology, one company’s booth featured “Mindart” technology. A passersby could answer a short series of prompts, and get a unique image based on the input made by generative AI. Entertainment aside, medically speaking, AI applications “are still research,” Riccardo Soffietti told his audience at one of several sessions devoted to AI. “But obviously, research is the future.”
Multiple sclerosis (MS) is and remains “a problem in the immune system” Stephen Sawcer told BioWorld. As in other autoimmune diseases, a faulty immune system attacks otherwise healthy tissues that it should be leaving alone. In the case of MS, the tissue in question is oligodendrocytes. And a study published online in Nature on June 28, 2023, suggests that while MS’ beginnings are autoimmune, the path it takes in an individual patient is determined in part by how well the brain can cope with the autoimmune attack.
B cells that expressed a constellation of checkpoint inhibitors could be spurred into antitumor activity by deleting or blocking the checkpoint molecule T-cell immunoglobulin and mucin domain 1 (TIM-1). The findings, which were published online in Nature on June 21, 2023, suggest ways to bring B cells into the antitumor fight. More broadly, Lloyd Bod told BioWorld, his laboratory aims to “break the dogma that B cells only produce antibodies.”
Back-to-back papers in the June 22, 2023, issue of Nature have identified separate molecular mechanisms underlying sex-specific cancer outcomes. Researchers from The University of Texas MD Anderson Cancer Center showed that increased expression of the epigenetic enzyme KDM5D, which is located on the Y chromosome, contributed to cancer progression in KRAS-mutated tumors. In the same issue of Nature, a team from Cedars-Sinai reported new insights into the consequences of losing the entire Y chromosome.
Part of the reason for CAR T cells’ astonishing success in B-cell cancers is that B cells are astonishingly easy to replace. CAR T cells are specific, yes. But they are not specific to tumor cells. They are specific to their target antigens. In the case of Yescarta (axicabtagene ciloleucel, Gilead Sciences Inc.) and Kymriah (tisagenlecleucel, Novartis AG), the first two clinically approved T cells, that target is CD19, which is expressed on B-cell precursors. And when it is successful, the treatment leaves patients without any B cells at all.