Development of an electrochemiluminescence-based ELISA method for the quantitative assessment of cleaved lamin A In order to accurately quantitate the amount of cleaved lamin A generated by caspase-6, we turned to an ELISA-based assay format using the MesoscaleH platform, which allows for a fast and sensitive detection with minimal background using electrochemi-luminescence [29] . To determine whether cleavage of lamin A is more sensitive than cleavage of the VEID peptide substrate in detecting low levels of active caspase-6, we incubated different concentrations of the enzyme in parallel either with Ac-VEID-AFC or purified lamin A protein and determined the amount of cleavage after 30 min by measuring the fluorescence in the sample (for Ac-VEID-AFC) or by subjecting the sample to an ELISA using the lamin A neo-epitope antibody (for lamin A cleavage). Comparison of the results showed that both assays perform at least equally well in detecting active caspase-6 concentrations down to 10 nM, with the lamin cleavage assay showing a linear concentration-response relationship down to the lowest caspase concentrations tested (Fig. 3A) . Signal-to-noise ratios were at or above 3 for the ELISA assay for as low as 10 nM caspase-6, whereas the signal-to-noise dropped below 3 for the VEID-based assay at this concentration (Fig. 3B ). Using a peptide inhibitor for caspase-6, VEID-CHO, both assays furthermore arrived at a similar IC 50 value (lamin-based ELISA: 64620 nM, VEID-based assay: 5666 nM), indicating that the ELISA method is suitable to assess the inhibition of caspase-6 by small molecules or peptides. Overall, our method shows a slight increase in sensitivity over commonly used VEID cleavage methods and is able to reliably detect caspase-6 concentrations down to 10 nM.