Current medicinal chemistry
-
Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α -galactosidase A which leads to progressive intracellular accumulation of globotriaosylceramide in tissues and organs including heart, kidney, vascular endothelium, the nervous system, the eyes and the skin. Cardiac involvement is common, leads to fatal complications and is mainly responsible for reduced life expectancy in Fabry disease. The exact staging of disease progression and timely initiation of treatment is essential in Fabry disease. Therefore, it is essential to use the possibilities of specific biomarkers for early detection of organ involvement or early diagnosis. ⋯ In conclusion, we suggest to measure lyso-GB3 and hsTNT at least once a year. The routine measurement of these two biomarkers will help now for the staging of every individual patient and in addition, will help for a better general understanding of Fabry disease.
-
Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. ⋯ The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apoC-III production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review, we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.