A Pan-Respiratory Antiviral Chemotype Targeting a Host Multi-Protein Complex.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious virus in multiple cell culture models for all six families of viruses causing most respiratory disease in humans. In animals this chemotype has been demonstrated efficacious for Porcine Epidemic Diarrhea Virus (a coronavirus) and Respiratory Syncytial Virus (a paramyxovirus).

Extraneurological sparing in long-lived typical Lafora disease.

Lafora disease (LD) clinically appears in previously healthy teenagers as progressively worsening seizures, myoclonus, dementia, and ultimately a vegetative state leading to death within a decade of its onset. Here we present a typical case of LD in which the patient survived until the age of 40. Although the patient's brain was severely affected, other organs remained functional until her death.

Efficacy and tolerability of perampanel in ten patients with Lafora disease.

Lafora disease (LD) is a fatal intractable adolescence-onset progressive myoclonus epilepsy. Recently, two single-case studies reported drastic reductions in seizures and myoclonus with the AMPA antagonist perampanel and improved activities of daily living. We proceeded to study the effect of perampanel on 10 patients with genetically confirmed LD with disease duration ranging from 2 to 27years.

PTG protein depletion rescues malin-deficient Lafora disease in mouse.

Ubiquitin ligases regulate quantities and activities of target proteins, often pleiotropically. The malin ubiquitin E3 ligase is reported to regulate autophagy, the misfolded protein response, microRNA silencing, Wnt signaling, neuronatin-mediated endoplasmic reticulum stress, and the laforin glycogen phosphatase. Malin deficiency causes Lafora disease, pathologically characterized by neurodegeneration and accumulations of malformed glycogen (Lafora bodies).