Translating Pathomechanisms into Treatment for Spinal Muscular Atrophies

项目总结

PROJECT SUMMARY Spinal muscular atrophies (SMAs) are monogenetic motor neuron (MN) diseases that cause debilitating muscle weakness and often early mortality. Our research program focuses on advancing therapeutics for two forms of SMA: proximal SMA caused by recessive, loss-of-function mutations of the survival motor neuron 1 gene (SMN1) and distal SMA (dSMA) caused by dominant mutations of the transient receptor potential vanilloid 4 gene (TRPV4). This administrative supplement to my R35 grant funded by the NINDS Landis Mentorship Award will provide funds to augment the mentorship and training of four graduate students at Johns Hopkins University School of Medicine with the long-term goal of fostering their future careers in biomedicine working to advance treatment for neurodegenerative diseases. Each student will pursue a graduate thesis project that is within the scope of research proposed in the parent R35 grant: Stephen Brown and Maddie Dent will focus on proximal SMA and Anna Bagnell and Jonathan Alevy will focus on distal SMA. They will leverage unique resources and state-of-the-art technologies to define factors limiting efficacy of current SMA therapeutics, characterize cellular and molecular mechanisms driving SMA pathology, and identify and validate novel therapeutic strategies. In order to foster their training, the first aim of the supplement is to provide regular one-on-one meetings for scientific discussion including review of relevant literature, hypothesis generation, experimental design, and data interpretation. The second aim to foster their training by enabling them to utilize cutting-edge experimental techniques to pursue their scientific hypotheses. The third aim is to support travel of students to scientific meetings for presentations and networking and the fourth aim is to create a rich community of trainees for “peer” mentoring.