BlueRock Therapeutics, in collaboration with Memorial Sloan Kettering Cancer Center, announced that the US FDA has cleared their Investigational New Drug application to proceed with a Phase I study in patients with advanced Parkinson’s disease (PD). This is the first trial in the US to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson’s disease.
[BlueRock Therapeutics (PR Newswire, Inc.)]
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Using an RNA-seq platform, scientists identified and validated the differential gene expression of five transcription factors that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson’s disease.
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Swaidan, N. T., Salloum-Asfar, S., Palangi, F., Errafii, K., Soliman, N. H., Aboughalia, A. T., Wali, A. H. S., Abdulla, S. A., & Emara, M. M. (2020). Identification of potential transcription factors that enhance human iPSC generation. Scientific Reports, 10(1), 21950. https://doi.org/10.1038/s41598-020-78932-9 Cite
Investigators showed proof of concept of human glial progenitor cells (hGPCs) conversion using fetal cells and also established a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro.
[Stem Cell Reports]
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Nolbrant, S., Giacomoni, J., Hoban, D. B., Bruzelius, A., Birtele, M., Chandler-Militello, D., Pereira, M., Ottosson, D. R., Goldman, S. A., & Parmar, M. (2020). Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.08.013 Cite
Seelos Therapeutics, Inc. announced the signing of a Sponsored Research Agreement with Duke University to use the MPTP-induced Parkinson’s Disease (PD) mouse model to establish in vivo proof-of-concept study to demonstrate that administration of LV-dCas9-DNMT3A virus can prevent and/or delay PD and test the efficacy and safety of SLS-004. Subsequently, other pre-clinical models would be utilized to further validate the investigational product.
[Seelos Therapeutics, Inc.]
Seelos Therapeutics, Inc. announced the signing of a Sponsored Research Agreement with Duke University to use the MPTP-induced Parkinson’s Disease (PD) mouse model to establish in vivo proof-of-concept study to demonstrate that administration of LV-dCas9-DNMT3A virus can prevent and/or delay PD and test the efficacy and safety of SLS-004.
[Seelos Therapeutics Inc.]
To elucidate the role of S-nitrosylated parkin and divalent metal transporter 1 in Parkinson’s disease, SH-SY5Y cells were transfected with parkin, being treated with S-nitrosoglutathione and 1-methyl-4-phenylpyridinium (MPP+).
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To explore the role of tristetraprolin in Parkinson’s disease (PD), an in vitro 1‐methyl‐4‐phenylpyridinium cell model and an in vivo 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine of PD were used.
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Sun, X., Zhang, H., Xie, L., Qian, C., Ye, Y., Mao, H., Wang, B., Zhang, H., Zhang, Y., He, X., & Zhang, S. (n.d.). Tristetraprolin destabilizes NOX2 mRNA and protects dopaminergic neurons from oxidative damage in Parkinson’s disease. The FASEB Journal, n/a(n/a). https://doi.org/10.1096/fj.201902967R Cite
Investigators examined the protective effect of noradrenaline against H2O2‐induced neurotoxicity using two different mixed cultures: the mixed culture of human astrocytoma U‐251 MG cells and human neuroblastoma SH‐SY5Y cells, and the mouse primary cerebrum mixed culture of neurons and astrocytes.
[Journal of Neuroscience Research]
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Yoshioka, Y., Negoro, R., Kadoi, H., Motegi, T., Shibagaki, F., Yamamuro, A., Ishimaru, Y., & Maeda, S. (n.d.). Noradrenaline protects neurons against H2O2-induced death by increasing the supply of glutathione from astrocytes via β3-adrenoceptor stimulation. Journal of Neuroscience Research, n/a(n/a). https://doi.org/10.1002/jnr.24733 Cite
The authors review existing protocols to generate human midbrain organoids, how they have been used so far to model Parkinson’s disease. address challenges inherent to organoid cultures, and discuss applicable strategies to dissect the molecular pathophysiology of the disease.
[Frontiers in Neurology]
The authors reveal an important role for astrocytes in Parkinson’s disease pathology and highlight the potential of iPSC-derived cells in disease modeling and drug discovery.
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Sonninen, T.-M., Hämäläinen, R. H., Koskuvi, M., Oksanen, M., Shakirzyanova, A., Wojciechowski, S., Puttonen, K., Naumenko, N., Goldsteins, G., Laham-Karam, N., Lehtonen, M., Tavi, P., Koistinaho, J., & Lehtonen, Š. (2020). Metabolic alterations in Parkinson’s disease astrocytes. Scientific Reports, 10(1), 14474. https://doi.org/10.1038/s41598-020-71329-8 Cite
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.