Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome.

Human-specific transcriptomic and regulatory features are present in the cerebellum, with ZP2 playing a key role in synapse regulation. ZP2 expression is induced by pontine mossy fibers, leading to decreased synaptic proteins and neuronal activity, which provides insights into the evolutionary development of the human cerebellum.

Optovolution leverages optogenetics and the yeast cell cycle to impose rapid, tunable selection, enabling the continuous evolution of light-responsive regulators, logic gates, and other complex protein behaviors that were previously difficult to evolve.

Integration of electrophysiology with single-cell transcriptomics defines the molecular signature of human dermal sleeping nociceptors and reveals oncostatin M as a selective modulator of these neurons in humans, providing a therapeutic entry point for neuropathic pain.