Dimethyl fumarate

Friedreich's Ataxia (FRDA) is a rare neurological disorder caused by an abnormal expansion of Guanine-Adenine-Adenine (GAA) repeat in intron 1 of the FXN gene, which encodes frataxin, leading to reduced expression of frataxin, a mitochondrial protein essential for cellular homeostasis. Frataxin deficiency results in oxidative stress and mitochondrial dysfunction and impaired redox balance. Currently, there is no cure for FRDA. This study aimed to evaluate the therapeutic potential of antioxidants dimethyl fumarate (DMF), N-acetylcysteine (NAC), and L-ascorbic acid (LAA) in restoring mitochondrial redox homeostasis and frataxin levels in FRDA patient-derived fibroblasts and 2D sensory neurons. We assessed cell viability, mitochondrial and cellular reactive oxygen species (ROS) levels, mitochondrial DNA copy number, mitochondrial membrane potential, and frataxin and NRF2 expression at both mRNA and protein levels following antioxidant treatment, either individually or in combination. Treatment with LAA, NAC, and DMF resulted in significant reductions in mitochondrial and cellular ROS, along with increased FXN and NRF2 expression, and enhanced NRF2 nuclear translocation. Furthermore, these compounds improved aconitase/citrate synthase activity, GSH/GSSG ratios, and mitochondrial membrane potential. Notably, the combination of LAA and NAC consistently alleviated multiple disease-associated defects in FRDA cells, suggesting its potential as a promising therapeutic approach.

In vitro diagnostics (IVD) is critical in disease screening and diagnosis. Point-of-care testing (POCT), which miniaturizes the IVD tests into portable chips and analyzers, offers the opportunity to decentralize the tests and obtain assay results on-site. Digital microfluidics (DMF) holds the merits of a small footprint, high automation, and low cost, making it a powerful tool for implementing various IVD assays for POCT settings. This review aims to consolidate the applications of DMF technology in different POCT settings and provide insights for DMF-based assay development. We first present the mechanism and fabrication processes of DMF technology. We then present its specific POCT applications, including infectious disease monitoring, neonatal disease screening, self-testing of chronic diseases, and routine disease screening. We further discuss the challenges in the development of DMF-based POCT technologies and provide an outlook on this exciting field.