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Translation in Brief

Gladstone-UCSF research center to focus on brain diseases; plus a mammography-based prediction algorithm, PharmaMar and an intracellular glycoprotein that blocks phagocytosis 

BioCentury’s roundup of translational news

BioCentury’s roundup of translational news.

Jan 30, 2021 | 2:54 AM GMT

Gladstone, UCSF pair up to tackle brain diseases
Scientists at the Gladstone Institutes and University of California San Francisco are launching the Gladstone-UCSF Center for Neurovascular Brain Immunology to develop treatments for neurological indications including Alzheimer’s and multiple sclerosis. Led by Katerina Akassoglou, the new center is supported by a $2.5 million donation from the Simon Family Trust and will focus on the intersection of the brain, immune and vascular systems.

Computational model to detect breast cancer risk
A deep-learning model, dubbed Mirai, uses mammography images to predict breast cancer risk. In a Science Translational Medicine publication, a team led by Massachusetts Institute of Technology scientists reported that Mirai’s concordance indices with training datasets ranged from 0.76 to 0.81. They also said that the algorithm was superior to two established prediction models when applied to a test dataset: in patients who would develop cancer within five years, Mirai correctly identified 41.5% of them as high risk compared with 36.1% for the Hybrid DL and 22.9% for the Tyrer-Cuzick models.

Blocking eukaryotic translation machinery to reduce SARS-CoV-2 replication
Researchers led by Icahn School of Medicine at Mount Sinai and UCSF scientists showed in Science that Aplidin plitidepsin was up to 27.5-fold more potent against SARS-CoV-2 in an HEK cell-based assay than Veklury remdesivir. The team had identified Aplidin’s target, EEF1A2, during research to find drug repurposing candidates for COVID-19, and PharmaMar S.A. (Madrid:PHM) began a clinical trial of Aplidin in March based on assays using the coronavirus HCoV-229E. In a Phase I trial, the small molecule translation factor inhibitor reduced viral loads by 70% in hospitalized COVID-19 patients. The Spanish company plans to begin Phase III testing in the near future. Gilead Sciences Inc. (NASDAQ:GILD) markets Veklury.

Mitochondrial protein interaction as phagocytosis checkpoint
An article in Cancer Cell from University of Michigan School of Medicine scientists revealed SCT1 as an intracellular phagocytosis checkpoint protein and showed that high tumor levels of the protein in patients with several types of cancer are associated with poor survival. SCT1 traps CALR, a mitochondrial “eat-me” signal, thereby inhibiting phagocytosis by antigen-presenting cells and impaired T cell activation. Tumor expression of SCT1 also enabled resistance to mAbs against PD-L1 in tumor-bearing mice.

TARGETS
CALR – Calreticulin
EEF1A1 (EEF1A) – Eukaryotic translation elongation factor 1 ɑ 1
PD-L1 (B7-H1) (CD274) – Programmed cell death 1 ligand 1
STC1 – Stanniocalcin 1

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