Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S.

Immunoglobulin mu-binding protein 2 () pathogenic variants lead to a spectrum of disorders characterized by alpha-motor neuron degeneration. We describe a compound heterozygous patient diagnosed with Charcot-Marie-Tooth disease type 2S with variants in : a pathogenic missense variant acting in with a confirmed intronic cryptic splice site variant. This variant was shown to result in the creation of a new splice acceptor site, loss of reading frame and nonsense-mediated decay.

On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships.

Functional human-on-a-chip systems hold great promise to enable quantitative translation to in vivo outcomes. Here, we explored this concept using a pumpless heart only and heart:liver system to evaluate the temporal pharmacokinetic/pharmacodynamic (PKPD) relationship for terfenadine. There was a time dependent drug-induced increase in field potential duration in the cardiac compartment in response to terfenadine and that response was modulated using a metabolically competent liver module that converted terfenadine to fexofenadine.