The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models.

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing.

Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction.

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice.

Early introduction of clinical skills improves medical student comfort at the start of third-year clerkships.

Background: To determine whether introducing clinical skills during the second year of medical school, via a competency-based College system approach, improves comfort level for medical students entering third-year clinical rotations.

Method: From 2003-2005, two cohorts of third-year medical students at the University of Washington were surveyed on their comfort level in the categories of history taking, physical examination, communication, and patient care.

Results: The cohort of students exposed to the College system reported a statistically significant greater comfort level in half of the measured areas, and in at least one area within each general category.