Medical Bulletin 30/ October/ 2024

Researchers at Baylor College of Medicine and Washington University School of Medicine in St. Louis have identified clinical and genetic predictors of multiply recurrent meningiomas (MRMs), a most aggressive form of this common brain tumor. Published in Science Advances, the study opens new opportunities for future development of potential biomarkers and therapeutic agents for these challenging tumors.

The team studied the tumors of 1,186 patients with primary meningiomas. Thirty-one of these primary tumors went on to be multiply recurrent meningiomas. The researchers compared clinical and genetic characteristics of multiply recurrent meningiomas with those of non-recurrent meningiomas (NRM). “We found that, compared to non recurrent meningiomas, multiply recurrent meningiomas are more numerous, larger and more common in men than in women,” said co-senior and co-corresponding author Dr. Akash J. Patel, associate professor of neurosurgery and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

The researchers analyzed the chromosomes of the tumors and found that multiply recurrent meningiomas have greater chromosomal instability and loss than non-aggressive meningiomas. “It has been well established that chromosomal instability is present in many human cancers and that increased instability has been associated with more aggressive cancers,” Patel said. In addition, the researchers found increased DNA methylation in multiply recurrent meningiomas genomes, an indication that the expression of certain genes is different in these tumors.

Reference: Sangami Pugazenthi et al., Multiomic and clinical analysis of multiply recurrent meningiomas reveals risk factors, underlying biology, and insights into evolution.Sci. Adv.10,eadn4419(2024).DOI:10.1126/sciadv.adn4419

A new study shows that a biomedical tool can successfully deliver genetic material to edit faulty genes in developing fetal brain cells. A complex transportation system with a revolutionary delivery method. The scientists found a way to deliver messenger RNA (mRNA) to cells that will be translated to functional proteins. This delivery method uses a unique lipid nanoparticle (LNP) formulation to carry mRNA. The objective is to introduce or transfect mRNA genetic material into the cells. The mRNA then would translate instructions to build proteins.

In a recent Nature Nanotechnology paper, Wang, Murthy and their team described a new lipid nanoparticle formulation to safely and efficiently deliver mRNA. lipid nanoparticle carrying mRNA need to arrive at the cells, where they will be taken in through a process known as endocytosis. There, the cell breaks the lipid nanoparticle carrier, which allows the mRNA cargo to be released. The study showed that the lipid nanoparticle method is more efficient at mRNA translation, reducing the need for potentially toxic doses.

The researchers injected the lipid nanoparticle with the mRNA into the fetal brain’s ventricles in a mouse model. The mRNA translates into CAS9, a protein that works like scissors for gene editing. The produced CAS9 will edit the gene responsible for Angelman syndrome. The study showed that the lipid nanoparticle tool was very efficient in delivering the mRNA that translated into CAS 9.

Using tracers, the researchers could see all the neurons that were edited inside the brain. Their study showed that the nanoparticles were taken up by the brain’s developing neural stem and progenitor cells. The nanoparticles led to gene edits in 30% of the brain stem cells in the mouse model. In the study, as the fetal development continued, the stem cells proliferated and migrated to form the central nervous system.

Reference: Widespread Gene Editing in the Brain via In Utero Delivery of mRNA Using Acid-Degradable Lipid Nanoparticles. Kewa Gao, Hesong Han, Matileen G. Cranick, Sheng Zhao, Shanxiu Xu, Boyan Yin, Hengyue Song, Yibo Hu, Maria T. Clarke, David Wang, Jessica M. Wong, Zehua Zhao, Benjamin W. Burgstone, Diana L. Farmer, Niren Murthy, and Aijun Wang. ACS Nano Article ASAP. DOI: 10.1021/acsnano.4c05169

A new study by researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, in collaboration with researchers at Harvard T.H. Chan School of Public Health and the Brown School of Public Health, examined a large sample of privately insured patients with obesity and found that use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as anti-obesity medications more than doubled from 2022 to 2023. During the same period, there was a 25.6% decrease in patients undergoing metabolic bariatric surgery to treat obesity. The study is published in JAMA Network Open.

Using a national sample of medical insurance claims data from over 17 million privately insured adults, the researchers identified patients with a diagnosis of obesity without diabetes in 2022-2023. The study found a sharp increase in the share of patients who received GLP-1 Receptor agonists during the study period, with GLP-1 receptor agonist use increasing 132.6% from the last six months of 2022 to the last six months of 2023. Meanwhile, there was a 25.6% decrease in use of bariatric metabolic surgery during the same period.

KEY TAKEAWAYS

Researchers from Mass General Brigham and collaborators assessed national trends in the number of patients with obesity prescribed GLP-1 drugs and the number who underwent metabolic bariatric surgery.

Researchers documented a 132.6% increase in patients prescribed GLP-1 drugs between 2022 and 2023, and a 25.6% decrease in patients undergoing bariatric surgery.

Only 6% of patients with obesity in the study population received either GLP-1 drugs or surgery, suggesting that many more patients could be receiving treatment.

Reference: Lin K et al. “Metabolic Bariatric Surgery in the Era of GLP-1 Receptor Agonists for Obesity Management” JAMA Network Open DOI: 10.1001/jamanetworkopen.2024.41380