Willbe.’s Post

Antisense therapies are the next generation of treatments for people with genetic and acquired diseases. These therapies work by using synthetic strands of nucleic acid (usually RNA) to target and inhibit specific gene expression, preventing the production of disease-causing proteins. Antisense oligonucleotides (ASOs) effectively bind to messenger RNA (mRNA) through complementary base pairing - blocking translation by preventing ribosomes from attaching to mRNA. Upcoming therapies in clinical trials Olpasiran/Pelacarsen: Reduces lipoprotein(a) levels to decrease the risk of atherosclerotic cardiovascular disease. Bepirovirsen: Targets hepatitis B virus for the treatment of chronic HBV. Antisense therapies will soon offer more effective treatments and improved outcomes for patients with limited treatment options in the coming years. #AntisenseTherapies #LipoproteinA #CardiovascularHealth

On November 15, 2024, the FDA approved Revuforj (revumenib), a first-in-class menin inhibitor, for patient with relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation. Rearrangements of the KMT2A gene (KMT2Ar) give rise to an aggressive form of acute leukemia that is associated with a very poor prognosis and high relapse rates. The KMT2Ar genetic abnormality is found in about 10% of acute leukemias. Revumenib works to treat KMT2Ar acute leukemias by blocking the interaction of both wild-type lysine methyltransferase 2A (KMT2A) and KMT2A fusion proteins with menin, a scaffold protein that controls gene expression and cell signaling. Revuforj Prescribing Information https://lnkd.in/eVSynACV Revuforj tablets are administered orally, twice daily, fasted or with a low-fat meal. #Cancer #Oncology #Revuforj #revumenib #Leukemia #AcuteMyeloidLeukemia #KMT2A #Moffitt #MoffittCancerCenter Moffitt Cancer Center

#SITC24 B7-H3 is categorized as a known immune checkpoint molecule, but its ligands remain largely unidentified, and its potential mechanisms of action are not yet well understood. In this context, the primary mechanism of action for B7-H3-targeting ADCs lies in payload-mediated cytotoxicity, as supported by the pharmacodynamic biomarker analysis from I-DXd clinical data. The lack of consistent changes in PD-L1-positive immune cell proportions or inflammatory gene signatures suggests that B7-H3 ADCs do not exert direct immunomodulatory effects on the tumor microenvironment.

A new study has found an interesting link between gene mutations in blood #cancer and #arthritis. The publication explains how specific gene mutations in blood cancer can impact autoimmune diseases such as seronegative RA. The study suggests that effective metabolic therapies in treating blood cancer may help arthritis patients.   → Conclusion: • IDH mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis. • High levels of 2-hydroxyglutarate mediate IDH-associated activation of innate immune response.   → Lih En Hong, Mihir D Wechalekar, and Devendra Hiwase led the research team at the Royal Adelaide Hospital in Australia for this study.    → Publication: Hong, Lih En, et al. "IDH Mutant Myeloid Neoplasms are Associated with Seronegative Rheumatoid Arthritis and Innate Immune Activation." Blood (2024).   📖 Read on…https://lnkd.in/egV5am-P   #Inflammation #Immunotherapy #DrugDevelopment

CAR-T and antibody therapy are two leading treatments for cancer. How do they compare to each other? Let's break it down. CAR-T - provides long-lasting immune responses - for some blood cancers, CAR-T have shown potential to completely cure the disease - where other options failed HOWEVER - They are more difficult to produce in large quantities (compared to antibody production) - In the tumor environment, they struggle to remain effective Therapeutic antibodies - Much easier to produce in large quantities - Some antibodies can interfere with receptors related to cell growth and blood vessel growth in tumors HOWEVER - Often, repeated administration is required (although some strategies are being developed to potentially fix that) - They often require other immune system components to be activated for their full effect to be appreciated I know I have them "competing" against each other here... But I'm excited to see combination therapies of these two treatments. For a curated list of content that simplifies the science of cell and gene therapy, check out #cgt_simplified Got any additional context to add here? Drop it in the comments. “Created with BioRender.com” #celltherapy #biotechnology #cartcelltherapy #antibodies #science

📃Scientific paper: Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease Abstract: BACKGROUND: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers. OBJECTIVE: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD. METHODS: Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra‐performance liquid chromatography tandem mass spectrometry. RESULTS: Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status. As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide. CONCLUSIONS: Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1‐PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. Continued on ES/IODE ➡️ https://etcse.fr/rS5 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease Abstract: BACKGROUND: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers. OBJECTIVE: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD. METHODS: Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra‐performance liquid chromatography tandem mass spectrometry. RESULTS: Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status. As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide. CONCLUSIONS: Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1‐PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. Continued on ES/IODE ➡️ https://etcse.fr/rS5 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Stay up-to-date with everything happening in biotech! Check out the most important news from last week below. 1️. Nobel Prize Win for microRNA Discovery Victor Ambros and Gary Ruvkun were awarded the 2024 Nobel Prize in Physiology or Medicine for uncovering the role of microRNAs in gene regulation, transforming our understanding of cellular processes. Learn more: https://lnkd.in/eBw3mwcV (Gen Eng News) 2️. Rwanda's Efforts Against Marburg Virus Rwanda is rigorously tracing and containing its first-ever Marburg virus outbreak. With vaccine trials on the horizon, the country is taking proactive measures to curb the spread. Learn more: https://lnkd.in/e4TZf49U (Scientific American) 3️. IGM Biosciences Shifts Focus from Cancer to Autoimmunity IGM pivots from oncology to autoimmune diseases, highlighting promising trials in rheumatoid arthritis and lupus, while restructuring its leadership team. Learn more: https://lnkd.in/e29Hcx2f (Fierce Biotech) 4️. FDA Greenlights First TCR Therapy for Solid Tumors Adaptimmune’s Tecelra receives FDA approval for synovial sarcoma, marking a milestone for engineered TCR therapies in tackling solid tumors. Learn more: https://lnkd.in/eUqcsRKU (Nature Magazine) 5️. Intellia Launches Late-Stage CRISPR Trial Intellia Therapeutics kicks off a Phase 3 trial for hereditary angioedema (HAE), testing its in vivo CRISPR-based treatment designed to provide a one-time solution. Learn more: https://lnkd.in/eT-ma8fh (BioPharma Dive) Which breakthrough excites you the most? Let us know in the comments, and follow us for more industry insights. #biotech #celltherapy #pharma #research #healthcare #innovation #insights

📃Scientific paper: Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease Abstract: BACKGROUND: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers. OBJECTIVE: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD. METHODS: Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra‐performance liquid chromatography tandem mass spectrometry. RESULTS: Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status. As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide. CONCLUSIONS: Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1‐PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. Continued on ES/IODE ➡️ https://etcse.fr/rS5 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease Abstract: BACKGROUND: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers. OBJECTIVE: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD. METHODS: Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra‐performance liquid chromatography tandem mass spectrometry. RESULTS: Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status. As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide. CONCLUSIONS: Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1‐PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. Continued on ES/IODE ➡️ https://etcse.fr/rS5 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.