👤 Muhana F Ilyas

Olezarsen emerged as a novel promising Apo-C3 inhibitor for dyslipidemia. However, its dose-response relationship remains uncertain. This review aims to evaluate the lipid-lowering effect of olezarsen, safety measures, and dose-response effects to determine the optimal dose. A systematic search was conducted across Scopus, PubMed, Science-Direct, and CENTRAL on January 2, 2025. Randomized controlled trial (RCT) comparing olezarsen with placebo in dyslipidemia was included. The Rob 2.0 tool was implemented to assess quality. R-studio and STATA were used to conduct statistical analysis. From a total of 194 documents at initial search, four RCTs involving 361 patients were included in the present analysis. Olezarsen significantly reduces plasma Apo-C3 across all dosage cohorts, including a 50 mg dose (MD: -70.31 %; 95 % CI: -83.89 to -56.74; p < 0.01) and an 80 mg dose administered every four weeks. It also significantly lowered triglycerides at any dose level, with reductions observed at 50 mg (MD: -49.84 %; 95 % CI = -70.42 to -22.37; p = 0) and 80 mg (MD: -52.32 %; 95 % CI: -58.25 to -46.40; p < 0.01). Olezarsen has minimal effect on low-density lipoprotein (LDL) but significantly increases high-density lipoprotein (HDL). Dose-response meta-analysis modeling suggests that 50 mg administered every four weeks may represent the optimal dose, beyond which added benefits diminish. Safety analysis revealed tolerability in liver, renal, and hematological parameters. In conclusion, olezarsen is an effective Apo-C3 inhibitor that improves lipid profiles with a favorable safety profile. This modeling-based insight refines previous findings by delineating a clearer therapeutic window. Show less

Bone morphogenetic proteins (BMPs) and the fibroblast growth factor receptor 1 (FGFR1) gene play essential roles in the development and maintenance of the skeletal system. Brachydactyly is a genetic condition characterized by shortened or missing bones in the hands and feet. Several types of brachydactyly have been identified, each associated with different genetic mutations. However, some cases do not fit into existing classifications, necessitating further genetic investigation. A 34-year-old female patient with an absent middle phalanx in the second digit of her left foot and her 13-year-old son, who presented with absent or malformed middle and distal phalanx in all ten toes, are evaluated. Whole Genome Sequencing (WGS) analysis identifies a missense variant (c.1073A >T; p.K358M) in the BMP8A gene and a novel missense variant (c.1787C >T, p.Ser596Phe) in the FGFR1 gene. Functional protein association network analysis demonstrates a strong association of BMP8A and FGFR1 with other brachydactyly disease-causing genes. Given that these mutations have not been previously linked to any recognized brachydactyly subtype, they likely define a distinct genetic condition. The findings suggest a novel form of brachydactyly, which naming is proposed as brachydactyly type AB. Show less

Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C and high-density lipoprotein cholesterol (HDL-C) through the bidirectional transfer of lipids. The novelty of CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering LDL-C strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, and obicetrapib, have reached late-stage clinical development for ASCVD risk reduction. Early trials failed to reduce atherosclerotic cardiovascular occurrences. Given the advent of some recent large-scale clinical trials (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting a meta-analysis is essential to investigate CETPis' efficacy. We conducted a thorough search of randomized controlled trials (RCTs) that commenced between 2003 and 2023; CETPi versus placebo studies with a ≥6-month follow-up and defined outcomes were eligible. major adverse cardiovascular events (MACEs), cardiovascular disease (CVD)-related mortality, all-cause mortality. stroke, revascularization, hospitalization due to acute coronary syndrome, myocardial infarction (MI). Nine RCTs revealed that the use of a CETPi significantly reduced CVD-related mortality (RR = 0.89; 95% CI: 0.81-0.98; Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI. Show less

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer related deaths globally. Despite advancements in treatment, drug resistance and adverse side effects have spurred the search for novel therapeutic strategies. This study aimed to investigate how the Show less