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Alzheimer’s Deficits in Neurogenesis and Memory Lessened by Small Molecule
Alzheimer’s Deficits in Neurogenesis and Memory Lessened by Small Molecule
May 26, 2021
Brains devastated by Alzheimer’s disease (AD) can be “rejuvenated” by restoring the expression of a microRNA molecule, report scientists based at the Leuven Brain Institute and the Netherlands Institute for Neuroscience (NIN). The molecule, miR-132, is one of the most consistently downregulated microRNAs in AD. According to the scientists, miR-132 loss in AD inhibits the generation of new neurons at the hippocampus, where memories are initially formed. The scientists added, however, that miR-132 supplementation can facilitate the generation of new neurons, and thereby alleviate memory deficits in AD.
The new findings appeared in Cell Stem Cell, in an article titled, “Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease.” The article begins by pointing out that adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. The article then described how AHN inhibition in a mouse model produces memory deficits. Finally, the article reported how “rescuing” AHN—by restoring miR-132—alleviates memory deficits in AD.
“[We] identify miR-132 as a potent regulator of AHN, exerting cell-autonomous proneurogenic effects in adult neural stem cells and their progeny,” the article’s authors wrote. “Using distinct AD mouse models, cultured human primary cells, established neural stem cells, and human patient material, we demonstrate that AHN is directly affected by AD pathology.”
The effects of miR-132 replacement, the authors concluded, corroborate “the significance of AHN in mouse models of AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.”
The presence of adult-born cells in the hippocampus of old people was recently demonstrated in scientific studies. It suggests that, generally speaking, the so-called process of adult neurogenesis is sustained throughout adulthood. Adult neurogenesis is linked to several aspects of cognition and memory in both animal models and humans, and it was reported to sharply decrease in the brains of patients with Alzheimer’s disease.
Researchers also found that higher levels of adult neurogenesis in these patients seem to correlate with better cognitive performance before death. “This could suggest that the adult-born neurons in our brain may contribute to a sort of cognitive reserve that could later on provide higher resilience to memory loss,” said Evgenia Salta, PhD, group leader at the NIN and a corresponding author of the new study.
“Seven years ago, while studying a small RNA molecule that is expressed in our brain, called miR-132, we came across a rather unexpected observation,” Salta continued. “This molecule, which we had previously found to be decreased in the brain of AD patients, seemed to regulate homeostasis of neural stem cells in the central nervous system.”
Back then, AD was thought to be a disease affecting only mature neuronal cells, so at first glance this finding did not seem to explain a possible role of miR-132 in the progression of AD. In this study, the researchers set out to address whether miR-132 can regulate adult hippocampal neurogenesis in healthy and Alzheimer’s brains. Using distinct AD mouse models, cultured human neural stem cells, and postmortem human brain tissue, the researchers discovered that miR-132 is required for the neurogenic process in the adult hippocampus.
“Decreasing the levels of miR-132 in the adult mouse brain or in human neural stem cells in a dish impairs the generation of new neurons. However, restoring the levels of miR-132 in AD mice rescues neurogenic deficits and counteracts memory impairment related to adult neurogenesis,” explained Sarah Snoeck, a technician in Salta’s group and a co-author of the current study.
These results provide a proof-of-concept regarding the putative therapeutic potential of bringing about adult neurogenesis in Alzheimer’s. “Our next goal,” Salta declared, “is to systematically assess the efficacy and safety of targeting miR-132 as a therapeutic strategy in AD.”
Moderna and Aldevron Expand Collaboration
Moderna and Aldevron Expand Collaboration
May 24, 2021
Officials at Moderna and Aldevron report that the companies have expanded their collaboration in support of Moderna’s COVID-19 vaccine and additional programs in Moderna’s clinical development pipeline. Aldevron will supply plasmid DNA (pDNA) to serve as the genetic template for generating the COVID-19 mRNA vaccine and other investigational programs in Moderna’s pipeline.
“Aldevron has been a long-standing partner of Moderna. We appreciate their collaboration and their expertise in the biologics space,” said Juan Andres, CTO and quality officer of Moderna. “We look forward to our ongoing work with this expanded partnership.”
“Aldevron’s support of the Moderna pipeline spans nearly a decade, and we’re incredibly proud of the trust they’ve placed in us” added Kevin Ballinger, CEO of Aldevron. “Our deep experience, coupled with enhanced operational efficiencies and recent capacity expansion place us in an excellent position to support Moderna’s efforts, especially during this critical time. We look forward to expanding our strategic partnership to serve a pipeline of important new programs in the future.”
Aldevron’s production of DNA continues to take place in its 70,000-sq- ft GMP facility located in Fargo, ND. Buildout and validation of an additional 189,000-sq-ft expansion to the GMP facility on Aldevron’s 14-acre Breakthrough Campus has been completed, enabling additional manufacturing capacity.
Ellen Shafer, senior director of marketing and communications at Aldevron, tells GEN that the company has invested substantially “in our capacity to provide the critical raw materials needed for gene and cell therapy and vaccine development.”
For example, Aldevron’s 45,000-sq-ft Advance Campus, newly opened in Fargo, focuses on the manufacture of pDNA for preclinical research programs. The Breakthrough Campus is now going through the validation process for GMP-S and GMP pDNA production and the build out of dedicated mRNA suites.
“And we cut the ribbon in February on a 7,000-sq-ft expansion space on our Madison Campus, which involves production labs for in vitro transcription enzymes and preclinical work in proteins, and are already looking to expand,” says Shafer.
Codagenix and Univercells Ink Vaccine Collaboration Agreement
Codagenix and Univercells Ink Vaccine Collaboration Agreement
May 21, 2021
Codagenix, a clinical-stage biotechnology company developing prophylactic vaccines and oncolytic virus therapies, and Univercells, signed a research collaboration agreement on an undisclosed, “high-priority” human vaccine target with global public health demand. The partnership will leverage Codagenix’s Synthetic Attenuated Virus Engineering (SAVE) platform for synthetic, live-attenuated virus vaccine development and Univercells’ viral vaccine process development and manufacturing capacity operated by Exothera, its CDMO.
Codagenix is developing a live-attenuated vaccine for which it has developed codon-pair deoptimized, attenuated virus cultured in Vero cells, according to the company. Univercells will assess the Codagenix vaccine candidate in Univercells Technologies’ (a Univercells company) scale-X™ bioreactor system, with commercial production feasibility foreseen on the NevoLine™ Upstream manufacturing platform, said Hugues Bultot, CEO of Univercells, adding that the scale-X single-use bioreactor is designed to deliver intensified production of viral products by relying on a novel structured fixed-bed design.
“The NevoLine platform, the latest equipment of Univercells Technologies, is designed to enable the scalable production of viral vectors resulting in high production throughput and lower long-term operational costs,” continued Bultot.
“Univercells’ viral vaccine manufacturing capabilities are the perfect fit for Codagenix as we expand our portfolio of vaccines developed using our SAVE platform, which utilizes a computer algorithm to recode the genomes of viruses and construct live-attenuated vaccines. This proprietary system enables Codagenix to transform a dangerous viral pathogen into a safe vaccine or solid-tumor therapeutic,” said J. Robert Coleman, PhD, CEO of Codagenix.
“Like COVI-VAC™, our single-dose, intranasal, live-attenuated vaccine against SARS-CoV-2, we believe the vaccine candidate now partnered with Univercells is well-positioned to address the shortcomings of existing interventions against a deadly global health challenge and—if successful—ensure large-scale availability at an affordable price.”
