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Quadriga BioSciences Initiates Clinical Trial of Innovative, Targeted Treatment for Brain Cancers

Quadriga BioSciences announced that the first patient has been dosed in a Phase I study of QBS10072S in patients with advanced malignancies.
[Quadriga BioSciences]
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Diversity and Function of Corticopetal and Corticofugal GABAergic Projection Neurons

Research conducted over the past 10 years has revealed that cortical GABAergic projection neurons are highly diverse in terms of molecular marker expression, synaptic targeting, activity pattern during distinct behavioural states and precise temporal recruitment relative to ongoing neuronal network oscillations.
[Nature Reviews Neuroscience]
Melzer, S., & Monyer, H. (2020). Diversity and function of corticopetal and corticofugal GABAergic projection neurons. Nature Reviews Neuroscience, 1–17. https://doi.org/10.1038/s41583-020-0344-9 Cite
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Modeling SHH-Driven Medulloblastoma with Patient iPS Cell-Derived Neural Stem Cells

Investigators found that Gorlin neuroepithelial stem (NES) cells formed tumors in mouse cerebellum mimicking human medulloblastoma. Retransplantation of tumor-isolated NES cells resulted in accelerated tumor formation, cells with reduced growth factor dependency, enhanced neurosphere formation in vitro, and increased sensitivity to Vismodegib.
[Proceedings of the National Academy of Sciences of the United States of America]
Susanto, E., Navarro, A. M., Zhou, L., Sundström, A., Bree, N. van, Stantic, M., Moslem, M., Tailor, J., Rietdijk, J., Zubillaga, V., Hübner, J.-M., Weishaupt, H., Wolfsberger, J., Alafuzoff, I., Nordgren, A., Magnaldo, T., Siesjö, P., Johnsen, J. I., Kool, M., … Wilhelm, M. (2020). Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1920521117 Cite
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MODAG Successfully Completes Phase 1 Study of their Lead Candidate Anle138b and Receives Additional USD 1.4 Million from Michael J. Fox Foundation

MODAG announced the successful completion of its first clinical trial of anle138b (NCT04208152) in healthy volunteers. Based on the positive Phase I study results, MODAG was also able to obtain additional funding of USD 1.4 million from The Michael J. Fox Foundation for parkinson’s research.
[MODAG]
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A Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury

Scientists showed that notch signaling-deficient astrocytes could generate new neurons after injury. Using single-cell RNA sequencing, they found that, when notch signaling was blocked, astrocytes transitioned to a neural stem cell-like state.
[Cell Stem Cell]
Zamboni, M., Llorens-Bobadilla, E., Magnusson, J. P., & Frisén, J. (2020). A Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.07.006 Cite
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Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury

The authors performed calcium imaging of neural stem/progenitor cell grafts in spinal cord injury sites in vivo and in adult spinal cord slices.
[Cell Stem Cell]
Ceto, S., Sekiguchi, K. J., Takashima, Y., Nimmerjahn, A., & Tuszynski, M. H. (2020). Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.07.007 Cite
AbstractGraphical Abstract

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Activation of a Neural Stem Cell Transcriptional Program in Parenchymal Astrocytes

Researchers used single-cell RNA sequencing to characterize neurogenesis by notch-depleted striatal astrocytes in vivo.
[eLife]
Activation of a neural stem cell transcriptional program in parenchymal astrocytes | eLife. (n.d.). Retrieved August 5, 2020, from https://elifesciences.org/articles/59733 Cite
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Pharmacologically Inhibiting Phosphoglycerate Kinase 1 for Glioma with NG52

Researchers developed a high-throughput screening and discovered that NG52, previously known as a yeast cell cycle-regulating kinase inhibitor, could inhibit the kinase activity of phosphoglycerate kinase 1.
[Acta Pharmacologica Sinica]
Wang, W., Jiang, Z., Hu, C., Chen, C., Hu, Z., Wang, A., Wang, L., Liu, J., Wang, W., & Liu, Q. (2020). Pharmacologically inhibiting phosphoglycerate kinase 1 for glioma with NG52. Acta Pharmacologica Sinica, 1–8. https://doi.org/10.1038/s41401-020-0465-8 Cite
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Purine Metabolism Regulates DNA Repair and Therapy Resistance in Glioblastoma

By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of glioblastoma, researchers find that purine metabolites, especially guanylates, strongly correlate with radiation resistance.
[Nature Communications]
Zhou, W., Yao, Y., Scott, A. J., Wilder-Romans, K., Dresser, J. J., Werner, C. K., Sun, H., Pratt, D., Sajjakulnukit, P., Zhao, S. G., Davis, M., Nelson, B. S., Halbrook, C. J., Zhang, L., Gatto, F., Umemura, Y., Walker, A. K., Kachman, M., Sarkaria, J. N., … Wahl, D. R. (2020). Purine metabolism regulates DNA repair and therapy resistance in glioblastoma. Nature Communications, 11(1), 3811. https://doi.org/10.1038/s41467-020-17512-x Cite
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Inhibition of miR-1193 Leads to Synthetic Lethality in Glioblastoma Multiforme Cells Deficient of DNA-PKcs

By implementing a highly efficient high-throughput screening platform using an in-house-constructed genome-wide human microRNA inhibitor library, scientists demonstrated that miR-1193 inhibition sensitized glioblastoma multiforme tumor cells with DNA-PKcs deficiency.
[Cell Death & Disease]
Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs | Cell Death & Disease. (n.d.). Retrieved August 5, 2020, from https://www.nature.com/articles/s41419-020-02812-3 Cite
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Cytovia Therapeutics Acquires Worldwide Rights to CytoImmune Therapeutics’ First-In-Class EGFR Dual-Targeting CAR for NK Cell Treatment of Glioblastoma & Other Solid Tumors

Cytovia Therapeutics, Inc announced that it has acquired worldwide rights from CytoImmune Therapeutics for its novel EGFR dual-targeting CAR to be used for NK cell therapy.
[Cytovia Therapeutics, Inc. (GlobeNewswire, Inc.)]
Press Release

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Pancreatic Ductal Adenocarcinoma Progression Is Restrained by Stromal Matrix

Experimentally manipulating stromal matrix with an anti– lysyl oxidase like-2 antibody in syngeneic orthotopic pancreatic ductal adenocarcinoma mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival.
[Journal of Clinical Investigation]
Jiang, H., Torphy, R. J., Steiger, K., Hongo, H., Ritchie, A. J., Kriegsmann, M., Horst, D., Umetsu, S. E., Joseph, N. M., McGregor, K., Pishvaian, M. J., Blais, E. M., Lu, B., Li, M., Hollingsworth, M., Stashko, C., Volmar, K., Yeh, J. J., Weaver, V. M., … Collisson, E. A. (2020). Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix. The Journal of Clinical Investigation, 130(9). https://doi.org/10.1172/JCI136760 Cite
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