Q-Cells (Glial cell-based therapeutic) / University of Utah, Q Therap - LARVOL DELTA

Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis (clinicaltrials.gov) - P1/2 | N=9 | Recruiting | Sponsor: Q Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Jul 2024

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Transplantation

Study to Investigate the Safety of the Transplantation (by Injection) of Human Glial Restricted Progenitor Cells (hGRPs; Q-Cells®) Into Subjects With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: Q Therapeutics, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Transplantation

Insights Into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury. (PubMed, Front Mol Neurosci) - "All approaches require a solid understanding of the molecular mechanisms guiding Schwann cell development and the repair phenotype, which we review herein. Together these studies provide essential context for current efforts to design glial cell-based therapies for peripheral nerve regeneration."

Journal • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain • Transplantation

Development, characterization, and applications of multi-material stereolithography bioprinting. (PubMed, Sci Rep) - "Finally, we constructed a simplified model of intratumoral heterogeneity with two separate sub-populations of 344SQ cells, which together grew over 14 days to form a dense regional interface. Together, these studies highlight the potential of multi-material stereolithography to probe heterotypic interactions between distinct cell types in tissue-specific microenvironments."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TGFB1

BRAF Controls the Effects of Metformin on Neuroblast Cell Divisions in C. elegans. (PubMed, Int J Mol Sci) - "We found that the neuronal Q-cells divisions were held at G1/S cell stage by metformin in vivo. Additionally, we demonstrated that metformin could reduce the phosphorylation activity of BRAF and block the BRAF-MAPK oncogenesis pathway to regulate neuronal Q-cell divisions during L1 arrest. This work discloses a new mechanism by which metformin treatment acts to promote neuronal cancer prevention, and these results will help promote the study of the anticancer mechanisms underlying metformin treatments."

Journal • Oncology • BRAF

[VIRTUAL] Developing Novel Targeted Therapies Using the High-Risk Vq Myeloma Model (ASH 2020) - "Importantly, VQ cells were resistant to some compounds currently used to treat MM, including the BCL-2 inhibitor Venetoclax, the alkylating agent Melphalan, and the topoisomerase II inhibitor Etoposide (red dots, Panel 1B)...Two compounds were chosen for further testing: the protein translation inhibitor Omacetaxine (Oma) based on its single agent efficacy, and the multi-receptor tyrosine kinase inhibitor Ponatinib (Pot) based on its high synergy with Tra...Taken together, our results show that low dose daily Trametinib treatment is superior to cycling dosage, and that Ponatinib treatment synergizes with both dosing schedules to extend survival in vivo. Our study demonstrates the utility of the VQ model for identifying new treatments for hrrMM and testing their efficacy in vivo. As part of our ongoing drug repurposing experiments, we have expanded our screening to a panel of 2,580 FDA-approved drugs, including but not limited to anti-cancer and anti-inflammatory drugs."

IO Biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • SDC1

Estrogen receptor α/prolactin receptor bilateral crosstalk promotes bromocriptine resistance in prolactinomas. (PubMed, Int J Med Sci) - "In the present study, increased levels of ERα and PRLR protein expression were detected in bromocriptine-resistant prolactinomas and MMQ cells. ERα inhibition abolished E2-induced PRLR upregulation and PRL-induced ERα phosphorylation, and fulvestrant, an ERα inhibitor, restored pituitary adenoma cell sensitivity to bromocriptine by activating JNK-MEK/ERK-p38 MAPK signaling and cyclin D1 downregulation. Collectively, these data suggest that the interaction between the estrogen/ERα and PRL/PRLR pathways may contribute to bromocriptine resistance, and therefore, that combination treatment with fulvestrant and bromocriptine (as opposed to either drug alone) may exert potent antitumor effects on bromocriptine-resistant prolactinomas."

Journal • Oncology • CCND1 • ER • MAPK8

Study to Investigate the Safety of the Transplantation (by Injection) of Human Glial Restricted Progenitor Cells (hGRPs; Q-Cells®) Into Subjects With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P1/2; N=30; Not yet recruiting; Sponsor: Q Therapeutics, Inc.; Trial completion date: Dec 2023 ➔ Dec 2024

Clinical • Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Transplantation

Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis (clinicaltrials.gov) - P1/2; N=9; Not yet recruiting; Sponsor: Q Therapeutics, Inc.; Trial completion date: Jun 2022 ➔ Jun 2024; Trial primary completion date: Jun 2022 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Transplantation

Multiple mechanisms underlie increased cardiac late sodium current. (PubMed, Heart Rhythm) - "The consistency between the late current produced in HEK, CHO, and hiPSC-CMs suggests late current is a feature of the SCN5A R1193Q variant in human cardiomyocytes, but that the mechanism by which the late current is produced is distinct, and indirect, compared to the more highly penetrant ΔKPQ. These data suggest observing a late current in an in vitro setting does not necessarily translate to highly pathogenic LQT3 phenotype but depends on underlying mechanism."

Journal • Atrial Fibrillation • Cardiovascular

[VIRTUAL] Lysine Acetylation of Aquaporin 3 Affects Water Permeability of the Collecting Duct (KIDNEY WEEK 2020) - " Following osmotic stimulus, we found AQP3Q/Q cells had the highest water permeability followed by the AQP3WT/WT cells and the AQP3R/R cells... Together, these preliminary data suggest that acAQP3 promotes localization to the basolateral membrane of the CD and supports the hypothesis that acAQP3 could serve as an important regulator of CD function in fluid homeostasis. Funding: NIDDK Support"

"⁦@ilovepathology⁩ ⁦@IHeartHisto⁩ ⁦@iheartpath⁩ ⁦@IHeartPathology⁩ ⁦@pembeoltulu⁩ ⁦⁦⁦@ChristineJKoMD⁩ ⁦@JMGardnerMD⁩ ; keratinflakes (sq cells) / not cornflakes , as clue to keratinous cyst in #FNA #Cytopathology" (@alaboudkhalid)

Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis. (PubMed, Cell Mol Immunol) - "ApoSQ-exposed CM from PTEN knockdown cells failed to enhance PTEN in 344SQ cells, restore cellular polarity, or exert anti-EMT and anti-invasive effects...PPARγ antagonist GW9662 reversed the signaling by PPARγ/PTEN; the reduction in EMT-activating transcription factors, such as Snai1 and Zeb1; and the antimetastatic effect of the ApoSQ injection. Thus, the injection of apoptotic lung cancer cells may offer a new strategy for the prevention of lung metastasis."

Journal • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Artesunate exerts anti-prolactinoma activity by inhibiting mitochondrial metabolism and inducing apoptosis. (PubMed, Ann Transl Med) - "ART accumulated in the mitochondria of MMQ cells, inhibiting mitochondrial respiratory function and mediating apoptosis through the mitochondrial pathway...ART has a strong inhibitory effect on prolactinoma both in vitro and in vivo, and its effects rely on high MMP to inhibit mitochondrial metabolism and induce apoptosis. Our results provide evidence for ART as a candidate drug for the treatment of prolactinoma."

Journal • Oncology • Psychiatry

"Q CELLS to Acquire Geli, Expanding Its Offerings in Integrated Energy Storage Solutions https://t.co/tO1USPDyTx" (@NewsFromBW)

Porcine epidemic diarrhea virus deficient in RNA cap guanine-N-7 methylation is attenuated and induces higher type I and III interferon responses. (PubMed, J Virol) - "Mutations to the S-adenosyl-l-methionine (SAM) binding motif in the nsp14 abolished the G-N-7 MTase activity and were lethal to PEDV...Notably, rPEDV-D350A induced significantly higher expression of both type I and III interferons in IPEC-DQ cells than the parental rPEDV...Here, we biochemically characterized G-N-7 MTase of PEDV nsp14 and found that G-N-7 MTase-deficient PEDV was defective in replication and induced higher type I and III interferons. These findings highlight that CoV G-N-7 MTase may be a novel target for rational design of live attenuated vaccines and antiviral drugs."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease

Glial cell: a potential target for cellular and drug based therapy in various CNS diseases. (PubMed) - Curr Pharm Des - "...Fingolimod is already being marketed for this disease, while guanabenz and ibudilast are facing clinical trials. Many researches revealed the role of glial cells in Alzheimer's disease, in which riluzole (a glutamate modulator already in market for amyotrophic lateral sclerosis-ALS) was found to be effective. Q-cells® are glial cell-based therapeutic agent to treat ALS that only produce astrocytes and oligodendrocytes, when transplanted in vivo...This barrier can be overcome by implanting a drug reservoir in brain parenchyma (wafer), by judicious selection of drug delivery system (nanoparticulate system), or by using an alternative route of administration (intranasal route). This review revolves around cellular and drug based modulation of glial cells to achieve maximum therapeutic benefit for some of the CNS diseases."

Journal • Alzheimer's Disease • Biosimilar • Complement-mediated Rare Disorders • Multiple Sclerosis • Oncology • Pain

The Charcot-Marie Tooth Disease Mutation R94Q in MFN2 Decreases ATP Production but Increases Mitochondrial Respiration under Conditions of Mild Oxidative Stress. (PubMed, Cells) - "Interestingly, these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells. We conclude that mitochondria harboring the disease-causing R94Q mutation in MFN2 are more susceptible to oxidative stress, which causes uncoupling of respiration and ATP production possibly by a less efficient mitochondrial quality control."

Journal • Gene Therapies • Genetic Disorders • Pain

The KBTBD6/7-DRD2 axis regulates pituitary adenoma sensitivity to dopamine agonist treatment. (PubMed, Acta Neuropathol) - "Dopamine agonists (DAs), such as cabergoline (CAB), have been successfully used in the treatment of prolactinomas...Knockdown of KBTBD6/7 sensitized MMQ cells and primary pituitary tumor cells to CAB treatment...Together, our findings have uncovered the novel mechanism of DRD2 protein degradation and shown that the KBTBD6/7-DRD2 axis regulates PA sensitivity to DA treatment. KBTBD6/7 may thus become a promising therapeutic target for pituitary tumors."

Journal • Oncology • Targeted Protein Degradation

DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma. (PubMed, Cancer Lett) - "DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a highly conserved kinase whose hyperactivation is critically involved in a variety of human tumors...Consistently, overexpression of DEPTOR inhibited pituitary tumor GH3 and MMQ cells proliferation in vitro and in vivo, and sensitized GH3 and MMQ cells to cabergoline (CAB), a dopamine agonist (DA)...Furthermore, DEPTOR enhanced autophagy-dependent cell death to confer cells sensitivity to CAB. Taken together, our results suggest that DEPTOR may be a potential target for the treatment of PAs."

Journal • Targeted Protein Degradation

Factors controlling floc formation and structure in the cyanobacterium Synechocystis sp. PCC 6803. (PubMed, J Bacteriol) - "A proportion of nonflocculating Δhfq cells can be incorporated into wild-type flocs, but the presence of a high proportion of Δhfq cells disrupts the large-scale architecture of the floc.IMPORTANCE Some bacteria form flocs, which are multicellular floating assemblages of many thousands of cells...The flocs have a characteristic structure based on strands of linked cells aggregating into dense clusters. Cells within the dense clusters show signs of nutrient stress, pointing to a disadvantage of floc formation."

Journal

Single-cell transcriptional landscapes reveal HIV-1-driven aberrant host gene transcription as a potential therapeutic target. (PubMed, Sci Transl Med) - "Single-cell transcriptome analysis of HIV-1 SortSeq cells revealed enrichment of nonsense-mediated RNA decay and viral transcription pathways...HIV-1-induced aberrant transcription was driven by the HIV-1 promoter as shown by CRISPR-dCas9-mediated HIV-1-specific activation and could be suppressed by CRISPR-dCas9-mediated inhibition of HIV-1 5' long terminal repeat. Overall, we identified cellular factors supporting HIV-1 reactivation and HIV-1-driven aberrant host gene transcription as potential therapeutic targets to disrupt HIV-1 persistence."

Journal • Gene Therapies • Infectious Disease • IL2 • JAK1

Bromocriptine and cabergoline induce cell death in prolactinoma cells via the ERK/EGR1 and AKT/mTOR pathway respectively. (PubMed, Cell Death Dis) - "In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma."

Journal

Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling. (PubMed, Biomolecules) - "In contrast, CHQ cells were equally responsive to myostatin, and follistatin remained unaltered...In conclusion, the effects of myostatin on intracellular signaling may be cell line- or organism-specific, and C2C12 myotubes seem to be a nonoptimal in vitro model for investigating the effects of myostatin on canonical and noncanonical signaling in skeletal muscle. This may be due to altered expression of activin receptor ligands and their regulators during muscle cell differentiation."

Journal • Preclinical

Generation of anterior hindbrain-specific, glial-restricted progenitor-like cells from human pluripotent stem cells. (PubMed, Stem Cells Dev) - "Notably, engrafted GPLCs not only differentiated into GFAP-positive astrocytes, but also myelinated the brains of adult shiverer mice 8 weeks after transplantation. Our strategy for establishing anterior hindbrain-specific GPLCs with gliogenic potency will facilitate their use in the treatment of demyelinating diseases and studies of the molecular mechanisms underlying glial development in the hindbrain."

Journal • CNS Disorders • Multiple Sclerosis • Oncology • Solid Tumor • Transplantation