A reassessment of spinal cord pathology in severe infantile spinal muscular atrophy: Reassessment of spinal cord pathology.

Aims: Spinal muscular atrophy (SMA) is a life-limiting paediatric motor neuron disease characterised by lower motor neuron loss, skeletal muscle atrophy and respiratory failure, if untreated. Revolutionary treatments now extend patient survival. However, a limited understanding of the foundational neuropathology challenges the evaluation of therapeutic success.

Onasemnogene-abeparvovec administration to premature infants with spinal muscular atrophy.

Twin girls born at 30 weeks' gestation with spinal muscular atrophy (SMA) received onsasemnogene-abeparvovec (OA) at 3.5 weeks of life. They had no treatment-related adverse events, normal acquisition of motor milestones, and normal neurological examination at 19 months.

Identifying tinnitus in mice by tracking the motion of body markers in response to an acoustic startle.

Rodent models of tinnitus are commonly used to study its mechanisms and potential treatments. Tinnitus can be identified by changes in the gap-induced prepulse inhibition of the acoustic startle (GPIAS), most commonly by using pressure detectors to measure the whole-body startle (WBS). Unfortunately, the WBS habituates quickly, the measuring system can introduce mechanical oscillations and the response shows considerable variability.

Combined clinical, structural, and cellular studies discriminate pathogenic and benign TRPV4 variants.

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear.